bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of potential vectors of and detection of antibodies against Rift Valley fever virus in livestock during interepizootic periods
Authors: Rostal Melinda K. , Evans Alina L. , Sang Rosemary , Gikundi Solomon , Wakhule Lilian , Munyua Peninah , Macharia Joseph , Feikin Daniel R. , Breiman Robert F. , Njenga M. Kariuki
Published: May 2010

Objective—To evaluate the prevalence of Rift Valley fever virus (RVFV) antibodies in livestock and presence of competent mosquito vectors of RVFV during an interepizootic period (IEP) in Kenya.

Animals—208 sheep and 84 goats ranging in age from 4 months to 15 years, from 2 breeding herds.

Procedures—Blood specimens were collected from the sheep and goats during the 1999–2006 IEP in Rift Valley Province, and serum was harvested. Serum specimens were tested for IgG and IgM antibodies against RVFV by use of an ELISA. In addition, 7,134 mosquitoes were trapped in Naivasha, Nairobi, and Northeastern Province, and speciation was performed.

Results—No animals were seropositive for IgM against RVFV. Of the animals born after the 1997–1998 epizootic, 18% (34/188) of sheep were seropositive for IgG against RVFV, compared with 3% (2/75) of goats. Seventy percent (8,144/11,678) of the mosquitoes collected were of the Culex subgenera; 18% (2,102/11,678) were Aedes spp.

Conclusions and Clinical Relevance—Detection of IgG in the sera of sheep and goats born after the 1997–1998 epizootic and before the 2006 epizootic indicated that virus activity existed during the IEP. Detection of Aedes mosquitoes, which are competent vectors of RVFV, suggested that a cryptic vector-to-vertebrate cycle may exist during IEPs.
Analysis of gene expression in brain tissue from Greyhounds with meningoencephalitis
Authors: Greer Kimberly A. , Daly Paul , Murphy Keith E. , Callanan John J.
Published: May 2010

Objective—To elucidate the pathogenesis of Greyhound meningoencephalitis by evaluating gene expression in diseased brain tissue.

Animals—Cadavers of 3 diseased (8- to 15-month-old) and 3 (10-month-old) control Greyhounds.

Procedures—Samples of RNA were extracted from brain tissue of all dogs and evaluated by use of a canine-specific microarray.

Results—A unique profile involving significant alterations in expression of 21 genes was evident in diseased dogs, compared with expression in control dogs. Most genes with up-regulated expression were related to immune function, with the remaining genes involved in ligand binding, signal transduction, transcriptional regulation, and formation and transportation of proteins including enzymes. Of notable involvement were genes encoding for major histocompatibility complexes, small inducible cytokine A5 precursor, myxovirus-resistant proteins, and components of the classical complement pathway, which are all genes common to pathways of viral infections and autoimmunity.

Conclusions and Clinical Relevance—Although results of microarray analysis did not clearly define a potential etiology of Greyhound meningoencephalitis, they did highlight a consistent gene alteration signature that would suggest a common etiology and pathogenesis for this condition.
Aqueous humor and plasma concentrations of ciprofloxacin and moxifloxacin following topical ocular administration in ophthalmologically normal horses
Authors: Clode Alison B. , Davis Jennifer L. , Salmon Jacklyn , LaFevers Heath , Gilger Brian C.
Published: May 2010

Objective—To determine the degree of ocular penetration and systemic absorption of commercially available topical ophthalmic solutions of 0.3% ciprofloxacin and 0.5% moxifloxacin following repeated topical ocular administration in ophthalmologically normal horses.

Animals—7 healthy adult horses with clinically normal eyes as evaluated prior to each treatment.

Procedures—6 horses were used for assessment of each antimicrobial, and 1 eye of each horse was treated with topically administered 0.3% ciprofloxacin or 0.5% moxifloxacin (n = 6 eyes/drug) every 4 hours for 7 doses. Anterior chamber paracentesis was performed 1 hour after the final dose was administered, and blood samples were collected at 24 (immediately after the final dose), 24.25, 24.5, and 25 hours (time of aqueous humor [AH] collection). Plasma and AH concentrations of ciprofloxacin or moxifloxacin were determined by use of high-performance liquid chromatography.

Results—Mean ± SD AH concentrations of ciprofloxacin and moxifloxacin were 0.009 ± 0.008 μg/mL and 0.071 ± 0.029 μg/mL, respectively. The AH moxifloxacin concentrations were significantly greater than those of ciprofloxacin. Mean ± SD plasma concentrations of ciprofloxacin were less than the lower limit of quantification. Moxifloxacin was detected in the plasma of all horses at all sample collection times, with a peak value of 0.015 μg/mL at 24 and 24.25 hours, decreasing to < 0.004 μg/mL at 25 hours.

Conclusions and Clinical Relevance—Moxifloxacin was better able to penetrate healthy equine corneas and reach measurable AH concentrations than was ciprofloxacin, suggesting moxifloxacin might be of greater value in the treatment of deep corneal or intraocular bacterial infections caused by susceptible organisms. Topical administration of moxifloxacin also resulted in detectable plasma concentrations.
Evaluation of nasolacrimal fluorescein transit time in ophthalmically normal dogs and nonbrachycephalic cats
Authors: Binder Daniel R. , Herring Ian P.
Published: May 2010

Objective—To evaluate fluorescein nasolacrimal transit (NLT) times in ophthalmically normal dogs and nonbrachycephalic cats by use of 2 methods of the Jones test.

Animals—73 dogs and 36 cats.

Procedures—Fluorescein dye was applied to the ocular surface of both eyes by means of a wetted fluorescein strip and, in a subsequent test, by administration of a drop of 0.2% fluorescein solution. During each test, the nares were monitored for the appearance of fluorescein for up to 30 minutes after application. Time of fluorescein appearance at the nares was recorded as NLT time. Recorded variables for all study animals included age, reproductive status, body weight, and Schirmer tear test values. For dogs, skull index, snout length, and cephalic conformation were also recorded. Data were grouped for statistical comparisons according to test results.

Results—In both dogs and cats, NLT was faster when the fluorescein solution versus fluorescein strip was used. In cats, none of the recorded variables had a significant effect on NLT, irrespective of the testing method used. In dogs, several variables had a significant effect on NLT, including cephalic conformation, snout length, age, and reproductive status, but these findings varied with testing method and testing group.

Conclusions and Clinical Relevance—NLT was highly variable in dogs and cats, regardless of testing method used. Assessment of nasolacrimal patency in brachycephalic dogs by use of either method evaluated here is not likely to be clinically useful. In cats, assessment of nasolacrimal patency with the fluorescein drop method was faster and more conclusive than with the fluorescein strip method.
Evaluation of biomarkers in bronchoalveolar lavage fluid for discrimination between asthma and chronic bronchitis in cats
Authors: Nafe Laura A. , DeClue Amy E. , Lee-Fowler Tekla M. , Eberhardt Jason M. , Reinero Carol R.
Published: May 2010

Objective—To compare concentrations of interleukin (IL)-4, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and total nitric oxide (NO) metabolites in bronchoalveolar lavage fluid (BALF) for discrimination between asthma and chronic bronchitis in cats.

Animals—97 cats.

Procedures—Cats screened with cytologic examination of BALF included 13 client-owned cats with naturally developing asthma, 8 client-owned cats with chronic bronchitis, 23 research cats with experimentally induced asthma, 33 research cats with experimentally induced nonseptic suppurative inflammation of the airways, and 20 healthy control cats. Banked unconcentrated BALF supernatant samples were assayed for concentrations of IL-4, IFN-γ, TNF-α, and total NO metabolites.

Results—Concentrations of IL-4 and IFN-γ in BALF were less than the limits of detection for most cats, precluding statistical analysis. No significant differences were detected among groups for TNF-α concentrations. Concentrations of total NO metabolites were significantly higher in cats with clinical chronic bronchitis, compared with research cats with nonseptic suppurative inflammation or research cats with asthma.

Conclusions and Clinical Relevance—There were no significant differences in tested biomarkers between cats with asthma and healthy control cats. None of the measured cytokines or NO metabolites were useful for discriminating between cats with naturally developing asthma and those with chronic bronchitis.
Expression of cyclooxygenase isoforms in ulcerated tissues of the nonglandular portion of the stomach in horses
Authors: Rodrigues Natália L. F. , Doré Monique , Doucet Michèle Y.
Published: May 2010

Objective—To characterize the expression of the cyclooxygenase (COX)-1 and COX-2 isoforms in naturally occurring ulcers of the nonglandular portion of the stomach in horses.

Specimen Population—38 specimens from ulcerated stomachs and 10 specimens from healthy stomachs.

Procedures—Specimens were collected at an abbatoir; for each specimen of squamous gastric mucosa, 1 portion was fixed in neutral-buffered 10% formalin for immunohistochemical analysis and another was frozen at −70°C for immunoblotting analysis. Immunoreactivity to 2 antibodies, MF241 (selective for COX-1) and MF243 (selective for COX-2), was evaluated by a veterinary pathologist using a scoring system. Expression of COX-1 and COX-2 was confirmed by use of immunoblotting analyses.

Results—All specimens from healthy stomachs strongly expressed COX-1, whereas only 2 of 10 expressed COX-2. The expression of both isoforms varied greatly in the ulcerated mucosal specimens. Expression of COX-1 was significantly lower and expression of COX-2 was significantly higher in ulcerated versus healthy specimens.

Conclusions and Clinical Relevance—Increased expression of COX-2 in gastric ulcers of the squamous portion of the stomach in horses suggested a role for this enzyme in gastric ulcer healing.
Clinical relevance of serial determinations of lactate dehydrogenase activity used to predict recurrence in dogs with lymphoma
Authors: Marconato Laura , Crispino Giampaolo , Finotello Riccardo , Mazzotti Silvia , Zini Eric
Published: May 2010

Objective—To evaluate whether serial determinations of serum lactate dehydrogenase (LDH) activity in dogs with lymphoma could be used to predict outcome and assist in early recognition of disease progression.

Design—Prospective cohort study.

Animals—50 dogs with lymphoma.

Procedures—LDH activity was determined in dogs with newly diagnosed lymphoma or that had not received treatment. The LDH activity was measured at time of initial diagnosis, at completion of chemotherapy, and at 1, 3, and 6 months after chemotherapy. Treatment response and recurrence were recorded. At the end of chemotherapy and at each time point thereafter, the proportion of dogs in complete remission with elevated LDH activity was compared between dogs that did or did not have recurrence within the successive 45 or 90 days. Use of the LDH activity at admission to predict disease-free and survival intervals was evaluated.

Results—The proportion of dogs in complete remission with increased LDH activity at completion of chemotherapy and at 1 month after chemotherapy with recurrence during the successive 45 days was significantly higher (3/9 and 7/9 dogs, respectively) than the proportion of dogs without recurrence (0/32 and 1/26 dogs, respectively). At 3 or 6 months, only 1 dog without recurrence within 45 days had increased LDH activity. Increased LDH activity at time of diagnosis was not associated with disease-free and survival intervals.

Conclusions and Clinical Relevance—Determination of LDH activity may help with identifying episodes of recurrence in dogs with lymphoma. Anticipation of recurrence is an appropriate reason to begin rescue treatment.
Laparoscopy for percutaneous tube cystostomy in dogs
Authors: Zhang Jian-Tao , Wang Hong-Bin , Shi Jiao , Zhang Nan , Zhang Shi-Xia , Fan Hong-Gang
Published: May 2010

Objective—To describe a laparoscopic technique for percutaneous tube cystostomy in dogs.

Design—Prospective cohort study.

Animals—8 healthy mixed-breed dogs.

Procedures—A laparoscope portal and 2 instrumental portals were created in the abdomen of anesthetized dogs that were in dorsal recumbency. Intracorporeal suturing was performed to place 2 simple interrupted sutures between the ventral body wall and urinary bladder. A purse-string suture was placed in the urinary bladder wall approximately 1 cm cranial to the 2 simple interrupted sutures. A stab incision was made into the urinary bladder in the middle of the purse-string suture; an 8F Foley catheter was inserted through the stab incision and into the urinary bladder. Two other sutures were placed between the ventral body wall and bladder 1 cm cranial to the Foley catheter to create a cystopexy. The Foley catheter was secured to the skin with a finger-trap suture and was attached to a closed urine collection bag. All dogs underwent follow-up laparoscopy 1 month later.

Results—Median time for laparoscopic percutaneous tube cystostomy was 85 minutes (range, 72 to 103 minutes); there were no major intraoperative or postoperative complications. On follow-up laparoscopy, focal fibrous adhesions between the ventral body wall and bladder were observed in all dogs and omentum attached to the cystopexy site was observed in 2 dogs.

Conclusions and Clinical Relevance—In this study, a laparoscopic percutaneous tube cystostomy was accomplished in healthy dogs by use of a 3-portal technique and appeared to be an effective and safe procedure.
Spontaneous hemoperitoneum in cats: 65 cases (1994–2006)
Authors: Culp William T. N. , Weisse Chick , Kellogg Melissa E. , Gordon Ira K. , Clarke Dana L. , May Lauren R. , Drobatz Kenneth J.
Published: May 2010

Objective—To describe the clinical signs, physical examination findings, clinical laboratory abnormalities, etiology, and outcome in cats with spontaneous hemoperitoneum.

Design—Retrospective case series.

Animals—65 client-owned cats with spontaneous hemoperitoneum.

Procedures—Medical records of cats with spontaneous hemoperitoneum at 7 large referral clinics were reviewed. Cats were included if a definitive diagnosis of spontaneous hemoperitoneum could be obtained from review of the medical records.

Results—65 cats met inclusion criteria. The most common historical findings were lethargy, anorexia, and vomiting. Common findings on physical examination included inadequate hydration status and hypothermia. The most common clinicopathologic abnormalities were high serum AST activity, anemia, prolonged prothrombin time, and prolonged partial thromboplastin time. Forty-six percent (30/65) of cats had abdominal neoplasia, and 54% (35/65) had nonneoplastic conditions. Hemangiosarcoma was the most often diagnosed neoplasm (18/30; 60%), and the spleen was the most common location for neoplasia (11/30; 37%). Eight cats survived to be discharged from the hospital. Cats with neoplasia were significantly older and had significantly lower PCVs than cats with non-neoplastic disease.

Conclusions and Clinical Relevance—Spontaneous hemoperitoneum in cats often results in debilitating clinical consequences. In contrast to dogs with hemoperitoneum, the cause of hemoperitoneum in cats is approximately evenly distributed between neoplastic and nonneoplastic diseases. Although only a few cats were treated in this study, the prognosis appears poor.
Physical and clinicopathologic findings in foals derived by use of somatic cell nuclear transfer: 14 cases (2004–2008)
Authors: Johnson Aime K. , Clark-Price Stuart C. , Choi Young-Ho , Hartman David L. , Hinrichs Katrin
Published: May 2010

Objective—To describe the health status of foals derived by use of somatic cell nuclear transfer (NT) at a university laboratory.

Design—Retrospective case series.

Animals—14 live-born NT-derived foals.

Procedures—Medical records from 2004 through 2008 were evaluated to identify all pregnancies resulting in live-born NT-derived foals. Information obtained included gestation length, birth weight, foaling complications, gross abnormalities of the fetal membranes, appearance of the umbilicus, mentation of the foal, limb deformities, and any other abnormalities detected in the neonatal period. Clinicopathologic data were also evaluated when available. Records of 4 recipient mares during gestation were included.

Results—Six foals were clinically normal for all evaluated variables. The most common abnormalities detected in the remaining 8 foals included maladjustment, enlarged umbilical remnant, and angular deformity of the forelimbs. Two foals died within 7 days after parturition; in the remaining foals, these conditions all resolved with medical or surgical management. Large offspring syndrome and gross abnormalities of the fetal membranes were not detected. The 12 surviving foals remained healthy.

Conclusions and Clinical Relevance—Associated problems of calves resulting from use of NT have been reported, but there are few data on the outcome of foals resulting from adult somatic cell NT in horses. Although this population of foals had a lower perinatal mortality rate than has been reported for NT-derived calves, some NT-derived foals required aggressive supportive care. Birth of foals derived from NT should take place at a center equipped to handle critical care of neonates.
The relative motion of membranes
Authors: Roberts Mark
Published: May 2010

The relative classical motion of membranes is governed by the equation (w β cα c r βa)a = R δγβα r gb x δa p aγ, where w is the hessian. This is a generalization of the geodesic deviation equation and can be derived from the lagrangian p · ṙ. Quantum mechanically the picture is less clear. Some quantizations of the classical equations are attempted so that the question as to whether the Universe started with a quantum fluctuation can be addressed.
Acute Heart Failure Due to Transient Left Ventricular Dyssynchrony: Case Study
Authors: Jourdain Matthieu , Bauchart Jean Jacques , Auffray Jean Luc , LeJemtel Thierry H. , Asseman Philippe , Ennezat Pierre Vladimir
Published: May 2010

This case study describes an unusual cause of acute heart failure that resolved with early beta-blockade therapy. A 52-year-old woman who had acute heart failure with severe left ventricular systolic dysfunction and left bundle branch block was admitted to a university medical center. Contrast-enhanced magnetic resonance images of the heart did not show any evidence of myocardial infarction or myocarditis. Rate-related left bundle branch block and subsequent left ventricular dyssynchrony resulted in acute systolic dysfunction that resolved with beta-blockade therapy that allowed heart rate control and narrowing of the QRS complex. Of note, the use of inotropic agents would have dramatically worsened the cardiac condition.
Preexisting Comorbid Psychiatric Conditions and Mortality in Nonsurgical Intensive Care Patients
Authors: Abrams Thad E. , Vaughan-Sarrazin Mary , Rosenthal Gary E.
Published: May 2010

Purpose To examine the effects of preexisting comorbid psychiatric conditions on mortality in a large cohort of patients admitted to a nonsurgical intensive care unit.

Methods This retrospective cohort study involved 66 672 consecutive eligible nonsurgical patients admitted to intensive care units in 129 Veterans Health Administration hospitals during 2005 and 2006. Preexisting comorbid psychiatric conditions were identified by using diagnoses from outpatient encounters in the prior year for depression, anxiety, psychosis, bipolar disorders, and posttraumatic stress disorder. Generalized estimating equations were used to adjust the risks of inhospital and 30-day mortality for demographics, comorbid medical conditions, markers of severity, and abnormal findings on laboratory tests at admission.

Results Comorbid psychiatric conditions were identified in 28% (n = 18 698) of patients. Patients with preexisting comorbid psychiatric conditions had lower (P < .001) unadjusted inhospital mortality (7.3% vs 8.7%) and 30-day mortality (10.0% vs 12.8%) than did patients without such conditions. After demographics, comorbid medical conditions, and severity were adjusted for, risk of in-hospital mortality among patients with comorbid psychiatric conditions was somewhat higher (odds ratio, 1.07, 95% confidence interval, 1.01–1.14; P = .02), although differences in 30-day mortality (odds ratio, 1.01, 95% confidence interval, 0.94–1.08; P = .70) were no longer significant.

Conclusion Preexisting comorbid psychiatric conditions are common among intensive care patients, but after comorbid medical conditions and severity were adjusted for, preexisting comorbid psychiatric conditions were not associated with a higher risk of 30-day mortality in a large national cohort of veterans.
Erbb2 DNA Vaccine Combined with Regulatory T Cell Deletion Enhances Antibody Response and Reveals Latent Low-Avidity T Cells: Potential and Limits of Its Therapeutic Efficacy
Authors: Rolla Simona , Ria Francesco , Occhipinti Sergio , Di Sante Gabriele , Iezzi Manuela , Spadaro Michela , Nicolò Chiara , Ambrosino Elena , Merighi Irene Fiore , Musiani Piero , Forni Guido , Cavallo Federica
Published: May 2010

Rat (r)Erbb2 transgenic BALB-neuT mice genetically predestined to develop multiple invasive carcinomas allow an assessment of the potential of a vaccine against the stages of cancer progression. Because of rErbb2 expression in the thymus and its overexpression in the mammary gland, CD8+ T cell clones reacting at high avidity with dominant rErbb2 epitopes are deleted in these mice. In BALB-neuT mice with diffuse and invasive in situ lesions and almost palpable carcinomas, a temporary regulatory T cells depletion combined with anti-rErbb2 vaccine markedly enhanced the anti-rErbb2 Ab response and allowed the expansion of latent pools of low-avidity CD8+ T cells bearing TCRs repertoire reacting with the rErbb2 dominant peptide. This combination of a higher Ab response and activation of a low-avidity cytotoxic response persistently blocked tumor progression at stages in which the vaccine alone was ineffective. However, when diffuse and invasive microscopic cancers become almost palpable, this combination was no longer able to secure a significant extension of mice survival.
Identification and Characterization of a Lupus Suppressor 129 Locus on Chromosome 3
Authors: Carlucci Francesco , Fossati-Jimack Liliane , Dumitriu Ingrid E. , Heidari Yasin , Walport Mark J. , Szajna Marta , Baruah Paramita , Garden Oliver A. , Cook H. Terence , Botto Marina
Published: May 2010

The 129-derived Sle16 is a susceptibility locus for systemic autoimmunity when present on the C57BL/6 (B6) background. Genetic analysis of a (129×B6)F2 cross identified a region from the B6 chromosome 3 (Sle18) with positive linkage to antinuclear Abs. In this study, we have generated a B6 congenic strain harboring the 129 allele of Sle18 and intercrossed this line with the lupus-prone B6.129-Sle16 strain. The presence of the 129-Sle18 allele in the B6.129-Sle16Sle18 double congenic mice suppressed the development of Sle16-mediated autoantibody production and ameliorated the renal pathology. The 129-Sle18 locus rectified the B cell abnormalities detected in the B6.129-Sle16 mice, such as the reduction in the percentage of marginal zone B and B1a cells and the increased number of germinal centers. The B6.129-Sle16Sle18 spleens still displayed an increased percentage of activated T and B cells. However, in the B6.129-Sle16Sle18 strain the percentage of naive T cells was equivalent to that in B6.129-Sle18 and B6 mice and these cells showed a reduced proliferative response to anti-CD3 stimulation compared with B6.129-Sle16 T cells. There was a significant increase in the percentage of CD4+FoxP3+regulatory T cells in all congenic strains. These cells had normal regulatory function when tested in vitro. Thus, 129-Sle18 represents a novel, non-MHC lupus-suppressor locus probably operating as a functional modifier of B cells that, in combination with other factors, leads to lupus resistance. Further characterization of this locus will help to uncover the immune mechanism(s) conferring protection against lupus.
Maintenance of Immune Tolerance to a Neo-Self Acetylcholine Receptor Antigen with Aging: Implications for Late-Onset Autoimmunity
Authors: Stacy Sue , Williams Earlanda L. , Standifer Nathan E. , Pasquali Amanda , Krolick Keith A. , Infante Anthony J. , Kraig Ellen
Published: May 2010

Age-related changes in immune regulation are likely to account for the age-associated increase in serum autoantibody levels and in certain autoimmune disorders, such as myasthenia gravis (MG). To demonstrate directly a loss of immune tolerance in older individuals, responses to the acetylcholine receptor, the autoantigen in MG, were assessed in transgenic mice expressing the Torpedo californica acetylcholine receptor (TAChR) α-chain as a neo-self Ag. T cells from young transgenic mice had been shown to be tolerant to p146–162, the TAChR α-chain peptide that dominated young nontransgenic T cell responses in vitro. The immunodominance of p146–162 was not lost with age; fine specificity was preserved. Moreover, T cell tolerance to p146–162, as well as to other epitopes of the TAChR α-chain extracellular domain, was maintained in old transgenic mice. Even multiple TAChR immunizations coupled with the MG-enhancing cytokine, IL-12, did not break tolerance. In addition, T cells exhibiting CD4 upregulation, an early activation marker, were reduced in frequency equivalently in old and young transgenic animals, suggesting that immune regulation in this model was not impacted by aging. Moreover, B cell tolerance was also maintained with age. The persistence of immune tolerance was accompanied by an increase in the proportion of T regulatory cells; it is speculated that this may compensate for deficiencies in central tolerance that occur owing to thymic involution. In summary, our study reveals, for the first time, that some immune tolerance mechanisms do survive aging; this suggests that certain late-onset autoimmune disorders may be induced by a specific insult that disrupts immune homeostasis.
Treatment of Autoimmune Arthritis Using RNA Interference-Modulated Dendritic Cells
Authors: Zheng Xiufen , Suzuki Motohiko , Ichim Thomas E. , Zhang Xusheng , Sun Hongtao , Zhu Fei , Shunnar Aminah , Garcia Bertha , Inman Robert D. , Min Weiping
Published: May 2010

Dendritic cells (DCs) have a dual ability to either stimulate or suppress immunity, which is primarily associated with the expression of costimulatory molecules. Ag-loaded DCs have shown encouraging clinical results for treating cancer and infectious diseases; however, the use of these cells as a means of suppressing immune responses is only recently being explored. Here, we describe the induction of RNA interference through administering short interfering RNA (siRNA) as a means of specifically generating tolerogenic DCs. Knockdown of CD40, CD80, and CD86, prior to loading DCs with the arthritogenic Ag collagen II, led to a population of cells that could effectively suppress onset of collagen-induced arthritis. Maximum benefits were observed when all three genes were concurrently silenced. Disease suppression was associated with inhibition of collagen II-specific Ab production and suppression of T cell recall responses. Downregulation of IL-2, IFN-γ, TNF-α, and IL-17 and increased FoxP3+ cells with regulatory activity were observed in collagen-induced arthritis mice treated with siRNA-transfected DCs. Collectively, these data support the use of ex vivo gene manipulation in DCs using siRNA to generate tailor-made tolerogenic vaccines for treating autoimmunity.
Scaffolding Adaptor Protein Gab1 Is Required for TLR3/4- and RIG-I–Mediated Production of Proinflammatory Cytokines and Type I IFN in Macrophages
Authors: Zheng Yuejuan , An Huazhang , Yao Ming , Hou Jin , Yu Yizhi , Feng Gensheng , Cao Xuetao
Published: May 2010

RIG-I–like helicases and TLRs are critical sensors in the induction of type I IFN and proinflammatory cytokines to initiate innate immunity against invading pathogens. However, the mechanisms for the full activation of TLR and RIG-I–triggered innate response remain to be fully investigated. Grb2-associated binder 1 (Gab1), a member of scaffolding/adaptor proteins, can mediate signal transduction from many receptors, however, whether and how Gab1 is required for TLR and RIG-I–triggered innate responses remain unknown. In this study, we demonstrated that Gab1 significantly enhances TLR4-, TLR3-, and RIG-I–triggered IL-6, IL-1β, and IFN-α/β production in macrophages. Gab1 knockdown in primary macrophages or Gab1 deficiency in mouse embryonic fibroblasts significantly suppresses TLR3/4- and RIG-I–triggered production of IL-6, IL-1β, and IFN-α/β. Consistently, Gab1 deficiency impairs vesicular stomatitis virus (VSV) infection-induced IFN-α/β production. In addition to promoting both MyD88- and TLR/IL-1 receptor domain-containing adaptor protein inducing IFN-β–dependent MAPKs and NF-κB activation, Gab1 enhances PI3K/Akt activation by directly binding p85 in TLR signaling and VSV infection. Accordingly, Gab1 inhibits VSV replication and VSV infection-induced cell damage by inducing type I IFNs and IFN-inducible gene expression via PI3K/Akt pathway. Therefore, Gab1 is needed for full activation of TLR3/4- and RIG-I–triggered innate responses by promoting activation of PI3K/Akt, MAPKs, and NF-κB pathways.
Acute Serum Amyloid A Induces Migration, Angiogenesis, and Inflammation in Synovial Cells In Vitro and in a Human Rheumatoid Arthritis/SCID Mouse Chimera Model
Authors: Connolly Mary , Marrelli Alessandra , Blades Mark , McCormick Jennifer , Maderna Paola , Godson Catherine , Mullan Ronan , FitzGerald Oliver , Bresnihan Barry , Pitzalis Costantino , Veale Douglas J. , Fearon Ursula
Published: May 2010

Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte/monocyte migration assays, invasion assays, and adhesion assays with or without anti–MCP-1/anti–IL-8. NF-κB was examined using a specific inhibitor and Western blotting. An RA synovial/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil–transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti–IL-8 or anti–MCP-1. A-SAA–induced chemokine expression was mediated through NF-κB in RA explants (p < 0.05). Finally, in the RA synovial/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.
Identification of a Novel Human MD-2 Splice Variant That Negatively Regulates Lipopolysaccharide-Induced TLR4 Signaling
Authors: Gray Pearl , Michelsen Kathrin S. , Sirois Cherilyn M. , Lowe Emily , Shimada Kenichi , Crother Timothy R. , Chen Shuang , Brikos Constantinos , Bulut Yonca , Latz Eicke , Underhill David , Arditi Moshe
Published: May 2010

Myeloid differentiation factor 2 (MD-2) is a secreted gp that assembles with TLR4 to form a functional signaling receptor for bacterial LPS. In this study, we have identified a novel alternatively spliced isoform of human MD-2, termed MD-2 short (MD-2s), which lacks the region encoded by exon 2 of the MD-2 gene. Similar to MD-2, MD-2s is glycosylated and secreted. MD-2s also interacted with LPS and TLR4, but failed to mediate LPS-induced NF-κB activation and IL-8 production. We show that MD-2s is upregulated upon IFN-γ, IL-6, and TLR4 stimulation and negatively regulates LPS-mediated TLR4 signaling. Furthermore, MD-2s competitively inhibited binding of MD-2 to TLR4. Our study pinpoints a mechanism that may be used to regulate TLR4 activation at the onset of signaling and identifies MD-2s as a potential therapeutic candidate to treat human diseases characterized by an overly exuberant or chronic immune response to LPS.
Resolution of Inflammation in Murine Autoimmune Arthritis Is Disrupted by Cyclooxygenase-2 Inhibition and Restored by Prostaglandin E2-Mediated Lipoxin A4 Production
Authors: Chan Marion Man-Ying , Moore Andrea Rossi
Published: May 2010

Acute inflammation follows defined phases of induction, inflammation and resolution, and resolution occurs by an active process that requires cyclooxygenase-2 (COX-2) activity. This study aims to address whether this paradigm extends to recognized model of chronic inflammation. We demonstrated that murine collagen-induced arthritis follows a similar sequential course. Interestingly, COX-2 and its metabolite, the presumably proinflammatory PGE2, are present in the joints during resolution, and blocking COX-2 activity and PGE2 production within this period perpetuated, instead of attenuated, inflammation. Repletion with PGE2 analogs restored homeostasis, and this function is mediated by the proresolving lipoxygenase metabolite, lipoxin A4, a potent stop signal. Thus, the study provided in vivo evidence for a natural, endogenous link between the cyclooxygenase–lipoxygenase pathways and showed that PGE2 serves as a feedback inhibitor essential for limiting chronic inflammation in autoimmune arthritis. These findings may explain the enigma regarding why COX-2 inhibitors are palliative rather than curative in humans, because blocking resolution may mitigate the benefit of preventing induction.
Monocyte Trafficking to Hepatic Sites of Bacterial Infection Is Chemokine Independent and Directed by Focal Intercellular Adhesion Molecule-1 Expression
Authors: Shi Chao , Velázquez Peter , Hohl Tobias M. , Leiner Ingrid , Dustin Michael L. , Pamer Eric G.
Published: May 2010

Recruitment of CCR2+Ly6Chigh monocytes to sites of infection is essential for efficient clearance of microbial pathogens. Although CCR2-mediated signals promote monocyte emigration from bone marrow, the contribution of CCR2 to later stages of monocyte recruitment remains unresolved. In this article, we show that CCR2 deficiency markedly worsens hepatic Listeria monocytogenes infection because Ly6Chigh monocytes are retained in the bone marrow. Intravenously transferred, CCR2-deficient Ly6Chigh monocytes traffic normally to hepatic foci of infection and contribute to bacterial clearance. Pertussis toxin treatment of adoptively transferred monocytes does not impair their intrahepatic trafficking, suggesting that chemokine signaling, once CCR2+Ly6Chigh monocytes emigrate from the bone marrow, is not required for monocyte localization to sites of bacterial infection in the liver. Expression of ICAM-1 is induced in close proximity to foci of bacterial infection in the liver, including on CD31+ endothelial cells, and blockade of CD11b and CD44 diminishes monocyte localization to these hepatic foci. Our studies demonstrated that Ly6Chigh monocyte recruitment from the bloodstream to the L. monocytogenes-infected liver does not require chemokine receptor-mediated signals but instead is principally dependent on integrin- and extracellular matrix-mediated monocyte adhesion.
Do personality characteristics and beliefs predict intra‐group bullying between prisoners?
Authors: Turner Polly , Ireland Jane L.
Published: April 2010

This study assesses how beliefs about aggression and personality can predict engagement in intra‐group bullying among prisoners. A sample of 213 adult male prisoners completed the DIPC‐SCALED (bullying behavior), the EXPAGG (beliefs toward aggression), and the IPIP (a five‐factor measure of personality). It was predicted that bullies would hold greater instrumental beliefs supporting the use of aggression than the other categories, with perpetrators reporting lower scores on agreeableness, conscientiousness, and openness to experience, and higher scores on neuroticism (i.e. low scores on emotional stability) than the remaining sample. Bullies and bully‐victims endorsed greater instrumental aggressive beliefs than the victim category. Only one perpetrator group, bullies were predicted by reduced levels of agreeableness and increased levels of neuroticism, whereas bully/victims were predicted by decreased levels of neuroticism. Limitations of this study and directions for future research are discussed. Aggr. Behav. 36:261–270, 2010. © 2010 Wiley‐Liss, Inc.
Ultrasound of the knee during voluntary quadriceps contraction: A technique for detecting otherwise occult effusions
Authors: Ike Robert W. , Somers Emily C. , Arnold Erin L. , Arnold William J.
Published: April 2010

Objective

To describe 1) a technique that can detect synovial effusions not seen on static ultrasound (US) examination and 2) the characteristics of patients with knee osteoarthritis (OA) for whom this technique proved useful.

Methods

From reviewed records of 76 patients with knee OA (112 knees) that we had seen for US‐guided injections over a defined period, we found 45 knees with no detectable effusion on static US, of which 18 (14 patients) showed fluid when scanned during voluntary quadriceps contraction. For all patients, we had recorded effusion features (physical examination, presence and size on US), and success of joint entry was determined by getting synovial fluid and/or seeing an air echo or inflow of injected material.

Results

The 14 patients we studied were obese (mean ± SEM body mass index 32.7 ± 2.3 kg/m2; 3 morbidly obese), with moderate to severe OA by radiography in most (Kellgren/Lawrence class 3 or 4 in 10 of 14 knees for which radiographs were available). The suprapatellar synovial space seen by US was small (mean ± SEM depth 0.38 ± 0.04 cm). Arthrocentesis obtained 0.5–16 ml of synovial fluid (mean ± SEM 2.9 ± 0.6 ml), which correlated with the depth of effusion as seen on US with the quadriceps in maximum contraction (Spearman's ρ = 0.5597, P = 0.0157). In 4 knees where arthrocentesis failed to retrieve fluid, we observed at injection the inflow of material and a linear air echo.

Conclusion

US of the knee during voluntary quadriceps contraction can find effusions not detectable on static US. Such effusions provide targets for accurate aspiration and injection that would not be appreciated with static US.
A catalytic CC bond‐forming reaction between aliphatic fluorohydrocarbons and arylsilanes
Authors: Lühmann Nicole , Panisch Robin , Müller Thomas
Published: May 2010

CC coupling reactions between arylsilanes and alkylfluorides are efficiently catalyzed by disilyl cation 1. Primary as well as secondary alkylfluorides were quantitatively coupled with arylsilanes; however, in the case of tertiary fluorides, the hydrodefluorination reaction predominated. Primary alkylfluorides were found to give arenes with mostly rearranged alkyl substituents. In all cases subsequent Friedel–Crafts‐type chemistry occurred. Copyright © 2010 John Wiley & Sons, Ltd.
Synthesis of phase‐pure SnS particles employing dithiocarbamate organotin(IV) complexes as single source precursors in thermal decomposition experiments
Authors: Menezes D. C. , de Lima G. M. , Carvalho F. A. , Coelho M. G. , Porto A. O. , Augusti R. , Ardisson J. D.
Published: April 2010

Preparation of tin(II) sulfide, semiconductor material, has been accomplished by thermal decomposition of easily prepared organotin dithiocarbamate complexes: [Sn{S2CNEt2}2Ph2] (1), [Sn{S2CNEt2}Ph3] (2), [Sn{S2CNEt2}3Ph] (3) and [Sn{S2CN(C4H8)}2Bu2] (4). Phase‐pure tin(II) sulfide has been obtained by pyrolysis of these precursors at 350 °C in N2. Thermogravimetric analysis, X‐ray powder diffraction, scanning electron microscopy, X‐ray electron probe microanalysis and 119Sn Mössbauer spectroscopy revealed that the complexes decompose in a single and sharp step (1 and 2), or in pseudo‐single stage (3 and 4), to produce SnS. We have also measured the bandgap energies of the residues using electronic spectroscopy in the solid state and the result relates well to that in the literature for SnS, 1.3 eV. A decomposition mechanism was also proposed for each complex based on electrospray ionization tandem mass spectrometric results. The synthetic method used in this work might be useful for the preparation of pure SnS on a large scale. Copyright © 2010 John Wiley & Sons, Ltd.
Effect of additive concentration and gamma radiation on the molecular and color properties of poly(vinyl chloride)
Authors: Nouh S. A. , Bahammam S.
Published: May 2010

The effects of addition of different monomers on the molecular properties of poly(vinyl chloride) (PVC) have been studied. Three different additive monomers from N‐phenyl maleimide derivatives were added with the same concentration 0.02 gm/1 gm PVC as stabilizers to PVC. These stabilizers are N‐phenyl maleimide, Para‐carboxy N‐phenyl maleimide, and Para‐amide carboxy N‐phenyl maleimide (PA‐NPMI). Their stabilizing efficiencies were evaluated by measuring the intrinsic viscosity of the solution samples. The results reveal that the type of the additive monomer plays a major role in determining the stabilizing potency of these materials. It was found that the PA‐NPMI is the most effective stabilizer that improves the intrinsic viscosity of pure PVC from 1.02 to 1.19. So, the effect of its addition with different concentrations was studied. The results indicate that the sample with 0.015 gm PA‐NPMI/1 gm PVC has higher intrinsic viscosity. Thus, this sample was chosen to be a subject for further study to investigate the effect of gamma irradiation on its molecular and color properties. Samples from the 0.015 gm PA‐NPMI/1 gm PVC were irradiated with gamma doses in the range 5–100 kGy. It is found that the irradiation in the dose range 20–60 kGy enhances the intrinsic viscosity of the samples. In addition, the transmission of these irradiated samples in the wavelength range 200–2500 nm, as well as any color changes, was studied. The color intensity ΔE was greatly increased with increasing the gamma dose, and was accompanied by darkness with a significant increase in the yellow color component. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
A novel organophosphorus flame retardant: Synthesis and durable finishing of poly(ethylene terephthalate)/cotton blends
Authors: Li Qiang‐Lin , Wang Xiu‐Li , Wang De‐Yi , Xiong Wei‐Cheng , Zhong Guang‐Hong , Wang Yu‐Zhong
Published: May 2010

A novel, hydroxy‐functional, organophosphorus flame retardant (FR), 2,2‐dihydroxymethylpropane‐1,3‐diolylbis(hydrogen phenylphosphonate) (DHDBP), was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy, 1H‐NMR, 13C‐NMR, 31P‐NMR, and elemental analysis. Subsequently, poly(ethylene terephthalate) (PET)/cotton (T/C; 70/30) blends were treated via pad‐dry‐thermosol finishing with DHDBP, citric acid, and a catalyst. Its flame retardancy, durability effect, and thermal decomposition behaviors were investigated by limited oxygen index, vertical burning test, thermogravimetric analysis, FTIR spectroscopy, and scanning electron microscopy. The results show that DHDBP was not only a reactive FR with a high efficiency but also a good char‐forming agent for the T/C blends. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Synthesis and characterization of polystyrene oligomers with several pendent epoxy groups
Authors: Zhang Jian , Huang Hui , Guan Yong , Wei Da‐Fu , Hu Fu‐Zeng , Zheng An‐Na , Xiao Hui‐Ning
Published: May 2010

Living polystyryl lithium was synthesized by anionic polymerization under the protection of argon at normal pressure, and styrene, toluene, tetrahydrofuran, and n‐butyllithium were used as a monomer, solvent, polar reagent, and initiator, respectively. Then, polystyrene oligomers containing several pendent epoxy groups with well‐defined structures and narrow molecular weight distributions (weight‐average molecular weight/number‐average molecular weight < 1.1) were prepared by the reaction of polystyryl lithium with glycidyl methacrylate. The prepared oligomers were characterized with gel permeation chromatography, Fourier transform infrared spectroscopy, 1H‐NMR, and the hydrochloric acid/dioxane argentimetric method. The effects of the glycidyl methacrylate dosage, molar mass of polystyrene precursors, copolymerization time, and temperature on the content of side epoxy groups were also investigated. The results confirm that 1,1‐diphenylethylene‐end‐capped polystyryl carbanion could initiate glycidyl methacrylate in toluene in the presence of lithium chloride and a small amount of tetrahydrofuran, and the content of the side epoxy groups could be adjusted. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Preparation and flame retardancy of 2‐EHA/n‐BA acrylic PSA containing single and combined flame retardants
Authors: Park Eun‐Young , Kim Ho‐Gyum , Lim Jeoung‐Cheol , Lee Dong‐Ho , Min Kyung‐Eun
Published: May 2010

UV curable acrylic PSAs (pressure‐sensitive adhesives) were modified with organic and inorganic flame retardants to improve flame retardancy of PSAs minimize the sacrifice of adhesion properties. The flame retardancy (UL‐94 test) of acrylic PSAs were enhanced by the addition of 5–30 wt % of an organic flame retardant such as TCEP (Tris(2‐chloroethyl)phosphate), PBPE (pentabromophenyl ether), and TBBPA(3,3′5,5′‐tetrabromobisphenol A). Especially, TBBPA is the best flame retardant for acrylic PSAs when it works alone. However, PSAs compounded with aluminum trihydroxide (Al(OH)3) showed a little reduction in burning time up to 30 wt %. An apparent synergic effect was observed only for an acrylic PSAs with a combination of TCEP and PBPE flame retardants. The addition of flame retardants brought a no significant effect on curing even in high amount. It was surmised that the miscibility between PSAs and flame retardant was closely related with flame retardancy and adhesion properties of acrylic PSAs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010