bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of soil concentrations of Rhodococcus equi and incidence of pneumonia attributable to Rhodococcus equi in foals on farms in central Kentucky
Authors: Cohen Noah D. , Carter Craig N. , Scott H. Morgan , Chaffin M. Keith , Smith Jacqueline L. , Grimm Michael B. , Kuskie Kyle R. , Takai Shinji , Martens Ronald J.
Published: March 2008

Objective—To determine whether soil concentrations of total or virulent Rhodococcus equi differed among breeding farms with and without foals with pneumonia caused by R equi.

Sample Population—37 farms in central Kentucky.

Procedures—During January, March, and July 2006, the total concentration of R equi and concentration of virulent R equi were determined by use of quantitative bacteriologic culture and a colony immunoblot technique, respectively, in soil specimens obtained from farms. Differences in concentrations and proportion of virulent isolates within and among time points were compared among farms.

Results—Soil concentrations of total or virulent R equi did not vary among farms at any time point. Virulent R equi were identified in soil samples from all farms. Greater density of mares and foals was significantly associated with farms having foals with pneumonia attributable to R equi. Among farms with affected foals, there was a significant association of increased incidence of pneumonia attributable to R equi with an increase in the proportion of virulent bacteria between samples collected in March and July.

Conclusions and Clinical Relevance—Results indicated that virulent R equi were commonly recovered from soil of horse breeding farms in central Kentucky, regardless of the status of foals with pneumonia attributable to R equi on each farm. The incidence of foals with pneumonia attributable to R equi can be expected to be higher at farms with a greater density of mares and foals.
Intraocular pharmacokinetics of intravenously administered marbofloxacin in rabbits with experimentally induced acute endophthalmitis
Authors: Regnier Alain , Schneider Marc , Concordet Didier , Toutain Pierre-Louis
Published: March 2008

Objective—To compare penetration of IV administered marbofloxacin in intraocular fluids of healthy and inflamed eyes in rabbits with endotoxin-induced endophthalmitis.

Animals—35 pigmented rabbits.

Procedures—Endophthalmitis was induced in the right eye via intravitreal administration of Escherichia coli endotoxin. The left eye was a control eye. After 24 hours, a single dose of marbofloxacin (4 mg/kg, IV) was administered. Groups of rabbits (n = 5/group) were euthanized 0.5, 1, 2, 4, 6, 10, and 18 hours later, and blood and ocular fluids were collected. Marbofloxacin concentrations were determined via reverse-phase high-performance liquid chromatography, and pharmacokinetic analysis of the data was performed with a mono-compartmental model.

Results—Mean area under the aqueous concentration-time curve was significantly lower in control eyes (1.64 ± 0.07 μg•h/mL) than in inflamed eyes (3.31 ± 0.11 μg•h/mL). Similarly, drug penetration into aqueous humor was 33% and 65% for control eyes and inflamed eyes, respectively. Mean area under the vitreous humor concentration-time curve for control eyes(1.75 ± 0.05 μg•h/mL) was significantly less than for inflamed eyes (2.39 ± 0.16 μg•h/mL). In the vitreous humor, corresponding penetrations were 34% and 47%, respectively.

Conclusions and Clinical Relevance—Penetration of marbofloxacin into the aqueous and vitreous humor after IV administration was significantly enhanced by intraocular inflammation, suggesting a role for this antimicrobial in the prophylaxis or treatment of bacterial endophthalmitis caused by susceptible pathogens.
Evaluation of a laparoscopic technique for collection of serial full-thickness small intestinal biopsy specimens in standing sedated horses
Authors: Bracamonte José L. , Bouré Ludovic P. , Geor Ray J. , Runciman John R. , Nykamp Stephanie G. , Cruz Antonio M. , Teeter Matthew G. , Waterfall Heather L.
Published: March 2008

Objective—To assess a technique for laparoscopic collection of serial full-thickness small intestinal biopsy specimens in horses.

Animals—13 healthy adult horses.

Procedures—In the ex vivo portion of the study, sections of duodenum and jejunum obtained from 6 horses immediately after euthanasia were divided into 3 segments. Each segment was randomly assigned to the control group, the double-layer hand-sewn closure group, or the endoscopic linear stapler (ELS) group. Bursting strength and bursting wall tension were measured and compared among groups; luminal diameter reduction at the biopsy site was compared between the biopsy groups. In the in vivo portion of the study, serial full-thickness small intestinal biopsy specimens were laparoscopically collected with an ELS from the descending duodenum and distal portion of the jejunum at monthly intervals in 7 sedated, standing horses. Biopsy specimens were evaluated for suitability for histologic examination.

Results—Mean bursting strength and bursting wall tension were significantly lower in the ELS group than in the hand-sewn and control groups in both the duodenal and jejunal segments. Use of the hand-sewn closure technique at the biopsy site reduced luminal diameter significantly more than use of the stapling technique. In the in vivo part of the study, all 52 biopsy specimens collected during 26 laparoscopic procedures were suitable for histologic examination and no clinically important perioperative complications developed.

Conclusions and Clinical Relevance—Laparoscopic collection of serial full-thickness small intestinal biopsy specimens with a 45-mm ELS may be an effective and safe technique for use in healthy adult experimental horses.
Radiographic determination of proventricular diameter in psittacine birds
Authors: Dennison Sophie E. , Paul-Murphy Joanne R. , Adams William M.
Published: March 2008

Objective—To establish an objective method of determining proventricular diameter in psittacine birds by assessment of lateral whole-body radiographic views.

Design—Retrospective case-control study.

Animals—100 parrots with no signs of gastric disease and 19 parrots with signs of gastric disease.

Procedures—Measurements were obtained for the following variables: proventricular diameter at the level of the junction between the last thoracic vertebra and synsacrum, maximum distance between the dorsal serosa of the proximal aspect of the proventriculus and dorsal border of the sternum, maximum coelomic cavity height at the level of the proximal aspect of the proventriculus, and maximum dorsoventral height of the keel of the sternum. The ratio of proventricular diameter to each of those measurements was calculated and compared among species within the group without signs of gastric disease and between the gastric and nongastric disease groups.

Results—No significant differences were seen among species of parrots without signs of gastric disease for any ratio, but there were significant differences between parrots with gastric signs and those without gastric signs for all ratios. Only the proventricular diameterto-maximum dorsoventral height of the keel of the sternum ratio had no numeric overlap between groups. Sensitivity and specificity of the ratio for detection of proventricular enlargement were both 100%. Six causes associated with proventricular enlargement were identified.

Conclusions and Clinical Relevance—Evaluation of the proventricular diameter-to-keel height ratio is a new method for evaluating proventricular size in psittacines. Ratio values < 0.48 indicate normal proventricular diameter and the absence of proventricular disease.
Ligneous conjunctivitis secondary to a congenital plasminogen deficiency in a dog
Authors: McLean Nancy S. Johnstone , Ward Daniel A. , Hendrix Diane V. H. , Donnell Robert L. , Ilha Marcia R. S.
Published: March 2008

Case Description—A 7-month-old 16.6-kg (36.5-lb) sexually intact female Golden Retriever was evaluated because of progressive severe bilateral membranous conjunctivitis, oral lesions, nasal discharge, and cough.

Clinical Findings—Histologic examination of conjunctival biopsy specimens revealed findings consistent with ligneous conjunctivitis. Circulating plasminogen activity was repeatedly low, and congenital plasminogen deficiency was identified as the underlying cause of the ocular, oral, and respiratory lesions.

Treatment and Outcome—Topical and subconjunctival administrations of fresh frozen plasma (FFP), topical administration of cyclosporine, and oral administration of azathioprine had no effect on the conjunctival membranes. Excision of the membranes followed by intensive treatment with topical applications of heparin, tissue plasminogen activator, corticosteroid, and FFP and IV administration of FFP prevented membrane regrowth. Intravenous administration of FFP increased plasma plasminogen activity to within reference limits, improved respiratory and oral lesions, and resulted in weight gain; discontinuation of this treatment resulted in weight loss, signs of depression, and worsening of lesions. After euthanasia because of disease progression, necropsy findings included mild hydrocephalus; multifocal intestinal hemorrhages; and fibrinous plaques in the oral cavity, nasopharynx, trachea, esophagus, and pericardium. Microscopically, the plaques were composed of fibrin and poorly organized granulation tissue. Fibrin thrombi were present within vessels in the lungs, oral cavity, and trachea.

Clinical Relevance—In dogs, congenital plasminogen deficiency can occur and may be the underlying cause of ligneous conjunctivitis. A combination of surgical and medical treatments may improve conjunctival membranes, and administration of FFP IV appears to be effective in treating nonocular signs of plasminogen deficiency.
Acute intrinsic renal failure in cats: 32 cases (1997–2004)
Authors: Worwag Stefanie , Langston Cathy E.
Published: March 2008

Objective—To determine patient demographics, clinicopathologic findings, and outcome associated with naturally acquired acute intrinsic renal failure (ARF) in cats.

Design—Retrospective case series.

Animals—32 cats with ARF.

Procedures—Cats were considered to have ARF if they had acute onset of clinical signs (< 7 days), serum creatinine concentration > 2.5 mg/dL (reference range, 0.8 to 2.3 mg/dL) and BUN > 35 mg/dL (reference range, 15 to 34 mg/dL) in conjunction with urine specific gravity < 1.025 or with anuria or increasing serum creatinine concentration despite fluid therapy and normal hydration status, and no signs of chronic renal disease. Cases were excluded if cats had renal calculi or renal neoplasia.

Results—Causes of ARF included nephrotoxins (n = 18 cats), ischemia (4), and other causes (10). Eighteen cats were oliguric. For each unit (mEq/L) increase in initial potassium concentration, there was a 57% decrease in chance of survival. Low serum albumin or bicarbonate concentration at initial diagnosis was a negative prognostic indicator for survival. Initial concentrations of BUN, serum creatinine, and other variables were not prognostic. Seventeen (53%) cats survived, of which 8 cats had resolution of azotemia and 9 cats were discharged from the hospital with persistent azotemia.

Conclusions and Clinical Relevance—Results suggested that survival rates of cats with ARF were similar to survival rates in dogs and that residual renal damage persisted in approximately half of cats surviving the initial hospitalization.
Comparison of methods to detect gastrointestinal parasites in llamas and alpacas
Authors: Cebra Christopher K. , Stang Bernadette V.
Published: March 2008

Objective—To compare relative sensitivity and overall yields of various methods of fecal examination for gastrointestinal parasites in llamas and alpacas.

Design—Prospective study.

Sample Population—Fecal samples from 42 alpacas and 62 llamas.

Procedures—Fecal samples were analyzed via direct smear, a modified McMaster technique with sucrose solution or saturated saline (approx 36% NaCl) solution, and a centrifugation-flotation procedure. McMaster flotation chambers were examined 15 and 60 minutes after loading. Centrifugation-flotation samples were examined after 10 and 60 minutes of flotation. The proportions of samples with positive results and concentrations of parasites were compared among methods.

Results—The centrifugation-flotation technique yielded more positive results than other methods for all parasites except small coccidia. Longer flotation time increased the proportion of positive results and parasite concentrations for all parasites except Nematodirus spp. Longer time in the McMaster chamber made little difference. By use of the modified McMaster technique, sucrose solution yielded more positive results for Trichuris spp, Eimeria macusaniensis, and strongyles, whereas saline solution yielded more positive results for Nematodirus spp and small coccidia. The saline solution McMaster test yielded more positive results for small coccidia than did most other methods, and the sucrose McMaster technique yielded more positive results for Trichuris spp.

Conclusions and Clinical Relevance—The centrifugation-flotation technique appeared to offer clear advantages in detecting infection with E macusaniensis, Trichuris spp, Nematodirus spp, and capillarids. The saline McMaster technique appeared to offer an advantage in detecting small coccidia.
Infection with Aleutian disease virus-like virus in a captive striped skunk
Authors: Allender Matthew C. , Schumacher Juergen , Thomas Kathy V. , McCain Stephanie L. , Ramsay Edward C. , James Evan W. , Wise Annabel G. , Maes Roger K. , Reel Danielle
Published: March 2008

Case Description—A 5-month-old captive female striped skunk (Mephitis mephitis) was evaluated because of lethargy, signs of depression, azotemia, and erythema of the skin around the eyes.

Clinical Findings—Antemortem diagnostic tests revealed renal disease but failed to identify an etiologic agent. A diagnosis of severe nonsuppurative interstitial nephritis was made on the basis of results of histologic examination of renal biopsy specimens.

Treatment and Outcome—The skunk was administered isotonic fluids SC daily and later every other day because of the handling-related stress. Because of the skunk's deteriorating condition, it was euthanized after 24 days of supportive care. Aleutian disease was diagnosed on the basis of positive results of a PCR assay that targeted the DNA from Aleutian disease virus (ADV); positive results for ADV were also obtained by use of plasma counterimmunoelectrophoresis and an ELISA. Genetic sequencing of the 365-base pair PCR product revealed 90% sequence identity with mink ADV.

Clinical Relevance—In the skunk of this report, infection with a skunk-specific parvovirus resulted in clinical signs and pathologic changes similar to those associated with ADV infection in mink. For skunks with signs of renal failure, differential diagnoses should include parvovirus infection. In confirmed cases of infection with this ADV-like virus, appropriate quarantine and biosecurity measures should be in place to prevent spread to other susceptible animals within a zoological collection.
Use of cytology as a diagnostic method in veterinary practice and assessment of communication between veterinary practitioners and veterinary clinical pathologists
Authors: Christopher Mary M. , Hotz Christine S. , Shelly Sonjia M. , Pion Paul D.
Published: March 2008

Objective—To determine the extent of use of cytology as a diagnostic method in veterinary practice and assess how veterinarians in practice communicate with veterinary clinical pathologists.

Design—Online survey.

Study Population—870 veterinarians.

Procedures—An online survey was made available to members of the Veterinary Information Network from October 1, 2004, through December 1, 2004.

Results—Respondents reported obtaining a median of 7 cytology samples weekly (range, 0 to 100). On average, respondents reported that 48.1% of the samples they collected were evaluated in-house, 29.5% were submitted to a veterinary diagnostic laboratory, and 21.6% were evaluated in-house and then submitted to a diagnostic laboratory. Most respondents (89.2%) reported using cytologic assessments to guide additional testing, and most (80.3%) indicated that they found the comments section of the cytology report to be the most important section. When asked to indicate the importance of various factors in their decision to use cytology as a diagnostic method, respondents overwhelmingly indicated that accuracy was very important. The most common reasons for consulting with a clinical pathologist were to discuss a discrepancy between clinical and cytologic findings, to clarify a diagnosis, and to ascertain the pathologist's confidence in a diagnosis. Respondents expressed more confidence in results when board-certified clinical pathologists were examining cytology samples than when others were.

Conclusions and Clinical Relevance—Results suggested that improving communication between veterinary practitioners and veterinary clinical pathologists could enhance the diagnostic value of cytologic examinations and improve clinical decision-making.
The Misleading Academic Discourse on Chinese–English Bilingual Education in China
Authors: Hu Guangwei
Published: March 2008

Although official promotion of content-based English language teaching started in mainland China only at the turn of the century, this form of language instruction, widely known in China as “Chinese–English bilingual education,” has gathered great momentum in the last 6 years and is now rattling across the country like a juggernaut. So-called Chinese–English bilingual education has always been controversial. Although small numbers of opponents have raised concerns about potential negative consequences and the constraints compromising optimistically envisioned goals, their voices have been drowned in the overwhelming academic discourse by a growing contingent of vocal advocates. This discourse is a driving force behind “the great leap forward” for Chinese–English bilingual education. This article problematizes the prevalent discourse on bilingual education in China. Based on analysis of systematically selected data sources, it contends that the academic discourse with its misconceptions, misrepresentations, and misinterpretations has misled stakeholders of bilingual education.
Surface and bulk properties of glycidyl methacrylate modified polypropylene: Experimental and molecular modeling studies
Authors: Verenich S. , Paul S. , Pourdeyhimi B.
Published: February 2008

Modifications of polypropylene (PP) are often carried out to either functionalize them or meet specific property demands. This study considered the process of PP grafting with glycidyl methacrylate (GMA) as an intermediate step to achieve improvements in surface properties of this polymer. Abundant literature is available on this grafting process but little is known about the surface properties of the grafted PP. Present work considered both experimental and computational approaches to attain this goal. Experimentally, it was established that the melting temperature of modified PP changed with the addition of GMA, and at higher concentrations of GMA in the PP matrix, heterogeneous nucleation took place. Experimental results revealed a decrease in the surface energy (SE) as well. To discern the underlying reasons behind these changes, molecular dynamics simulations were undertaken. The computational results revealed that the changes in SE could be associated with the location of the functional group. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Effects of the composition and nematic–isotropic phase transition on the electro‐optical responses of unaligned polymer‐dispersed liquid crystals. I. Composites of poly(methyl methacrylate) and E8
Authors: Deshmukh R. R. , Malik M. K.
Published: February 2008

Composite films composed of poly(methyl methacrylate) (PMMA) and the nematic‐type liquid crystal (LC) E8 were prepared by solution casting in chloroform. The electro‐optical performance characteristics were studied for a wide range of PMMA/E8 compositions (10–80 wt % E8). At two specific levels of LC (70 and 80 wt %), the effects of temperature, voltage, and frequency of the applied electric field on the optical transmittance of films were extensively measured with a He–Ne laser (λ = 632.8 nm) as a light source. Scanning electron microscopy observations showed the formation of large E8 droplets in PMMA due to phase separation, and the homogeneous distribution increased with increasing E8 content. The results were interpreted in terms of aggregation structure, interfacial interaction, LC loading, and the solubility of LC in the polymer matrix. The results obtained indicate that under the experimental conditions imposed, the output could be continuously controlled to the desired level by the selection of a suitable loading of LC to prepare polymer‐dispersed LC electro‐optical active composite films with response times on the order of only a few milliseconds. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Progression of carotid intima‐media thickness and plaque in women with systemic lupus erythematosus
Authors: Thompson Trina , Sutton‐Tyrrell Kim , Wildman Rachel P. , Kao Amy , Fitzgerald Shirley G. , Shook Betsy , Tracy Russell P. , Kuller Lewis H. , Brockwell Sarah , Manzi Susan
Published: March 2008

Objective

Women with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). The goals of this study were to determine the extent of atherosclerotic progression among women with SLE compared with a group of healthy controls and to determine whether factors attributed to SLE or its treatment were associated with atherosclerotic progression independent of traditional CVD risk factors.

Methods

A longitudinal study of women with SLE from the Pittsburgh Lupus Registry was conducted. Women 18 years of age and older (n = 217) underwent carotid ultrasound at baseline and at followup, an average of 4.19 years later. Clinical, serologic, and SLE‐related factors, and disease treatment were evaluated. Outcomes were changes in carotid intima‐media thickness (IMT) and plaque. Progression of CVD in a sample of women without lupus was used for comparison.

Results

The patients' mean ± SD age at baseline was 45.1 ± 10.3 years, and the mean ± SD IMT progression rate was 0.011 ± 0.03 mm per year. After controlling for traditional CVD risk factors, higher serum creatinine levels were associated with IMT progression (P = 0.0006). Plaque prevalence was 31% at baseline and 40% at followup; plaque progression occurred in 27% of the patients. Higher serum C3 levels and immunosuppressant use at baseline were related to plaque progression (P = 0.04 and P = 0.02, respectively) independent of traditional CVD risk factors. The plaque progression rate was higher than, and the IMT progression rate was similar to, those in the control group.

Conclusion

SLE patients have accelerated plaque progression compared with controls. SLE‐related risk factors are associated with the progression of IMT and plaque after controlling for traditional CVD risk factors. Carotid B‐mode ultrasound may serve as a surrogate end point in SLE intervention trials and clinically to track SLE management.
Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease
Authors: Lau Andrew C. , Duong Trang T. , Ito Shinya , Yeung Rae S. M.
Published: March 2008

Objective

Kawasaki disease (KD) is a multisystem vasculitis leading to damage in the coronary circulation and aneurysm formation. Because cardiac tissue from affected children is not available, investigation of the mechanisms responsible for coronary artery damage in KD requires use of a disease model. The present study was undertaken to examine, in an experimental model, the role of matrix metalloproteinase 9 (MMP‐9) on coronary artery inflammation and vascular damage.

Methods

C57BL/6 mice were injected with Lactobacillus casei cell wall extract to induce coronary arteritis. Hearts were isolated and assayed for MMP‐9 protein expression and enzymatic activity by immunoblotting or confocal microscopy and zymography, respectively. MMP‐9–deficient mice were used to examine the necessity of MMP‐9 for disease development.

Results

Localized inflammation at the coronary artery led to elastin breakdown and aneurysm formation. This occurred in the absence of smooth muscle cell apoptosis. Following disease induction, there was an increase in the amount and enzymatic activity of MMP‐9, an elastolytic protease. MMP‐9 was up‐regulated by tumor necrosis factor α (TNFα) and produced primarily by vascular smooth muscle cells. In MMP‐9–deficient animals, vascular inflammation continued to develop, but the incidence of elastin breakdown was significantly reduced. Elastin breakdown in the coronary artery was virtually eliminated by ablation of MMP‐9.

Conclusion

These findings show that TNFα up‐regulates expression of MMP‐9, an important proteinase responsible for extracellular matrix breakdown, leading to coronary artery damage in this model of KD. These results have important implications regarding treatments for improving coronary outcome in affected children.
Anakinra improves sensory deafness in a Japanese patient with Muckle‐Wells syndrome, possibly by inhibiting the cryopyrin inflammasome
Authors: Yamazaki Takashi , Masumoto Junya , Agematsu Kazunaga , Sawai Nobukuni , Kobayashi Shinji , Shigemura Tomonari , Yasui Kozo , Koike Kenichi
Published: March 2008

Muckle‐Wells syndrome (MWS) is a dominantly inherited autoinflammatory syndrome. Patients with MWS have a mutation in CIAS1, the gene encoding cryopyrin, a component of the inflammasome that regulates the processing of interleukin‐1β (IL‐1β). In this report we describe an 8‐year‐old Japanese girl with MWS who had symptoms of periodic fever, urticarial rash, conjunctivitis, arthropathy, and sensory deafness. Laboratory analysis of the patient's serum showed abnormally high concentrations of C‐reactive protein, serum amyloid A, and IL‐1β, and she had a heterozygous mutation in the CIAS1 gene, with C‐to‐T transversion at nucleotide position 778, encoding an arginine‐to‐tryptophan mutation at position 260 (R260W). Mononuclear cells (MNCs) isolated from the patient secreted large amounts of IL‐1β, without stimulation, and were highly sensitive to muramyldipeptide and lipopolysaccharide. After treatment with anakinra, laboratory results normalized, and clinical symptoms, including sensory deafness, disappeared, while MNCs appeared to remain activated. Thus, our case suggests that anakinra possibly affects the cryopyrin inflammasome and markedly improves the clinical and laboratory manifestations of MWS.
ADAM‐12 (meltrin α) is involved in chondrocyte proliferation via cleavage of insulin‐like growth factor binding protein 5 in osteoarthritic cartilage
Authors: Okada Aiko , Mochizuki Satsuki , Yatabe Taku , Kimura Tokuhiro , Shiomi Takayuki , Fujita Yoshinari , Matsumoto Hideo , Sehara‐Fujisawa Atsuko , Iwamoto Yukihide , Okada Yasunori
Published: March 2008

Objective

ADAMs are a gene family of multifunctional proteins. We undertook this study to determine which ADAM species is up‐regulated in osteoarthritic (OA) cartilage and to examine its pathobiologic function.

Methods

Expression of the 13 different metalloproteinase‐type ADAMs was screened by reverse transcription–polymerase chain reaction (PCR), and expression levels of prototype membrane‐anchored ADAM‐12 (ADAM‐12m) were determined by real‐time PCR. ADAM‐12m expression in articular cartilage was examined by in situ hybridization, immunohistochemistry, and immunoblotting. Chondrocytes were used for functional analyses of ADAM‐12m.

Results

ADAM‐12m was selectively expressed in 87% of OA cartilage, and the expression level was significantly higher in OA cartilage than in normal cartilage. In situ hybridization showed that OA chondrocytes were responsible for the expression. ADAM‐12m was immunolocalized on the membranes of OA chondrocytes, and its immunoreactivity correlated directly with the Mankin score and with degrees of chondrocyte cloning and proliferation. Immunoblotting analysis of OA chondrocytes demonstrated an active form of ADAM‐12m. ADAM‐12m expression in OA chondrocytes was selectively enhanced by transforming growth factor β (TGFβ), which also induced chondrocyte proliferation and degradation of insulin‐like growth factor binding protein 5 (IGFBP‐5). TGFβ‐induced chondrocyte proliferation was inhibited by suppression of IGF‐1 signaling. In addition, TGFβ‐induced chondrocyte proliferation, chondrocyte cloning in agarose gel culture, and digestion of IGFBP‐5 were inhibited with ADAM inhibitor, anti–ADAM‐12 antibody, and small interfering RNA for ADAM‐12.

Conclusion

These data suggest a novel function of ADAM‐12m in chondrocyte proliferation and cloning in OA cartilage through enhanced bioavailability of IGF‐1 from the IGF‐1–IGFBP‐5 complex by selective IGFBP‐5 digestion.
Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis
Authors: Guo Yongzhi , Li Jinan , Hagström Elin , Ny Tor
Published: March 2008

Objective

To assess the functional roles of plasmin in a murine model of Staphylococcus aureus–induced bacterial arthritis.

Methods

Bacterial arthritis was induced in plasminogen‐deficient (Plg−/−) and wild‐type (Plg+/+) littermates by local injection of 1 × 106 colony‐forming units of S aureus into the knee joints. Human plasminogen was administered to Plg−/− mice on days 0–7 or days 7–14. Antibiotic treatment was administered to Plg−/− mice on days 7–14. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed.

Results

In Plg+/+ mice, S aureus counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, S aureus was still detectable in all injected joints from Plg−/− mice, and bacteria counts were 27 times higher than the amount injected on day 0. The extent of macrophage and neutrophil recruitment to the infected joints was comparable for Plg+/+ and Plg−/− mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg−/− mice, however. Treatment of Plg−/− mice with antibiotic (cloxacillin) resulted in successful killing of the bacteria, but the necrotic tissue remained in the infected joints. When human plasminogen was given intravenously to Plg−/− mice daily for 7 days, bacterial clearance was greatly improved as compared with their untreated counterparts, and the amount of necrotic tissue in the joint cavity was dramatically reduced. The expression of interleukin 6 (IL‐6) and IL‐10 was higher in Plg+/+ mice than in Plg−/− mice during bacterial arthritis.

Conclusion

Our findings indicate that plasmin plays a pluripotent role in protecting against S aureus–induced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression.
Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon‐α–producing antigen‐presenting cells
Authors: Yan Bing , Ye Shuang , Chen Guangjie , Kuang Miao , Shen Nan , Chen Shunle
Published: March 2008

Objective

To explore whether there are extrinsic factors that impair the suppressive function of CD4+,CD25+ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE).

Methods

We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4+,CD25+,FoxP3+ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real‐time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon‐α (IFNα) in supernatants from the function assays were determined with an IFN‐stimulated response element–luciferase reporter assay.

Results

The percentage of CD4+,CD25+, FoxP3+ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean ± SEM 9.11 ± 0.73% versus 4.78 ± 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4+,CD25+ T cell subset from SLE patients as compared with controls. Antigen‐presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4+,CD25+ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFNα derived from SLE patient APCs.

Conclusion

We suggest that blockade of Treg cell–mediated suppression by IFNα‐producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease.
Does tumor necrosis factor α inhibition promote or prevent heart failure in patients with rheumatoid arthritis?
Authors: Listing Joachim , Strangfeld Anja , Kekow Jörn , Schneider Matthias , Kapelle Andreas , Wassenberg Siegfried , Zink Angela
Published: March 2008

Objective

To determine the hazard risk of developing or worsening heart failure in rheumatoid arthritis (RA) patients treated with tumor necrosis factor α (TNFα) inhibitors.

Methods

RA patients ages 18–75 years who started treatment with infliximab, etanercept, or adalimumab (n = 2,757), or conventional disease‐modifying antirheumatic drugs (controls; n = 1,491) at the time of enrollment in a German biologics register were studied. Cox proportional hazards models were applied to investigate the influence of disease‐related and treatment‐specific risk factors on the incidence or worsening of heart failure.

Results

The 3‐year incidence rates of heart failure in patients with and patients without cardiovascular disease at the start of treatment were 2.2% and 0.4%, respectively. After adjustment for traditional cardiovascular risk factors, an increased risk of developing heart failure was found in patients who had a higher 28‐joint Disease Activity Score at followup (hazard ratio [HR] 1.47 [95% confidence interval 1.07–2.02], P = 0.019). A residual nonsignificant risk related to treatment with TNFα inhibitors remained (adjusted HR 1.66 [95% confidence interval 0.67–4.1], P = 0.28). This residual risk was balanced by the efficacy of the anti‐TNF treatment. When only baseline characteristics were taken into account, the HR related to TNFα inhibitor treatment decreased to 0.70 (95% confidence interval 0.27–1.84).

Conclusion

The findings of this study indicate that TNFα inhibitor treatment that effectively reduces the inflammatory activity of RA is more likely to be beneficial than harmful with regard to the risk of heart failure, especially if there is no concomitant therapy with glucocorticoids or cyclooxygenase 2 inhibitors. Furthermore, the data suggest that TNFα inhibition does not increase the risk of worsening of prevalent heart failure.
Induction of macrophage secretion of tumor necrosis factor α through Fcγ receptor IIa engagement by rheumatoid arthritis–specific autoantibodies to citrullinated proteins complexed with fibrinogen
Authors: Clavel Cyril , Nogueira Leonor , Laurent Laetitia , Iobagiu Cristina , Vincent Christian , Sebbag Mireille , Serre Guy
Published: March 2008

Objective

Macrophage‐derived tumor necrosis factor α (TNFα) is a dominant mediator of synovitis in rheumatoid arthritis (RA). This study was undertaken to assess whether and how immune complexes (ICs) formed by the interaction of disease‐specific autoantibodies to citrullinated proteins (ACPAs) with their main synovial target antigen, citrullinated fibrin, contribute to TNFα production by macrophages.

Methods

An in vitro human model was developed in which monocyte‐derived macrophages were stimulated with ACPA‐containing ICs that were generated by capturing ACPAs from RA sera on immobilized citrullinated fibrinogen. Cellular activation was evaluated by TNFα assay in culture supernatants. Selective blockade of IC interactions with the 3 classes of Fcγ receptors (FcγR) was used to assess the contribution of each receptor to macrophage activation. In addition, 2 citrullinated fibrin–derived peptides bearing major ACPA epitopes were tested for their capacity to inhibit formation of macrophage‐activating ACPA‐containing ICs.

Results

ACPA‐containing ICs induced a dose‐dependent TNFα secretion by macrophages from 14 of 20 healthy donors. The macrophage response was systematically higher than that of the paired monocyte precursors. TNFα secretion was not reduced by blockade of FcγRI or FcγRIII, but was strongly repressed when interaction of ICs with FcγRII was prevented. The 2 citrullinated peptides significantly inhibited ACPA reactivity to citrullinated fibrinogen and, when tested together, almost completely abolished formation of macrophage‐activating ICs, thereby diminishing the secreted TNFα levels.

Conclusion

Our model demonstrates the inflammatory potential of ACPA‐containing ICs via engagement of FcγRIIa at the surface of macrophages, strongly supporting their pathophysiologic involvement. Continuing dissection of these molecular pathways could open the way to new therapeutic approaches in patients with RA.
Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse
Authors: Ward Benjamin D. , Furman Bridgette D. , Huebner Janet L. , Kraus Virginia B. , Guilak Farshid , Olson Steven A.
Published: March 2008

Objective

Posttraumatic arthritis is a frequent long‐term complication of intraarticular fractures. A model of a closed intraarticular fracture in C57BL/6 mice that progresses to posttraumatic arthritis has been developed. The MRL/MpJ mouse has shown unique regenerative abilities in response to injury. The objective of this study was to determine if the MRL/MpJ mouse is protected from posttraumatic arthritis after intraarticular fractures.

Methods

Intraarticular fractures were created in MRL/MpJ mice and C57BL/6 control mice (n = 16 each). Limbs were analyzed for posttraumatic arthritis 4 and 8 weeks after fracture using microfocal computed tomography bone morphology, subchondral bone thickness evaluation, and histologic evaluation of cartilage degeneration. Serum cytokines and biomarkers were measured after the mice were killed.

Results

Intraarticular fractures were successfully created in all 32 mice. In the experimental fractured limbs, C57BL/6 mice had a decrease in bone density, increased subchondral bone thickness, and increased cartilage degeneration compared with normal contralateral control limbs. In the MRL/MpJ mice, no differences in bone density, subchondral bone thickness, or histologic grading of cartilage degeneration were seen between fractured and contralateral control limbs. Cytokine analysis showed lower systemic levels of the proinflammatory cytokine interleukin‐1α (IL‐1α) and higher levels of the antiinflammatory cytokines IL‐4 and IL‐10 in the MRL/MpJ mice.

Conclusion

This study shows that the MRL/MpJ mouse is relatively protected from posttraumatic arthritis after intraarticular fracture. Further investigation into the mechanism involved in this response will hopefully provide new insight into the pathogenesis, prevention, and treatment of posttraumatic arthritis after intraarticular fracture.
Leishmanial lipid suppresses tumor necrosis factor α, interleukin‐1β, and nitric oxide production by adherent synovial fluid mononuclear cells in rheumatoid arthritis patients and induces apoptosis through the mitochondrial‐mediated pathway
Authors: Majumdar Kajal Nayan , Banerjee Aditi , Ratha Jagnyeswar , Mandal Mriganka , Sarkar Rathindra Nath , Saha Krishna Das
Published: March 2008

Objective

Leishmanial lipid is a strong immunosuppressor of host cells. Inhibition of the inflammatory responses of synovial cells through induction of apoptosis is one of the main targets of therapeutic intervention in rheumatoid arthritis (RA). This study was undertaken to examine the antiinflammatory and apoptosis‐inducing effects of leishmanial lipid on adherent synovial fluid mononuclear cells (SFMCs) in patients with RA.

Methods

Lipid was extracted from a Leishmania donovani promastigote (MHO/IN/1978/UR6) by the Bligh and Dyer method. Nitric oxide (NO) was measured using the Griess reaction, and enzyme‐linked immunosorbent assays for cytokines, NF‐κB, and cytochrome c were performed. Levels of cytokines, inducible nitric oxide synthase, caspases, Bcl‐2, Bax, t‐Bid, and cytochrome c in the cell lysate and of NF‐κB p65 in the nucleus were determined by Western blotting. Microscopic analysis, nuclear staining, DNA fragmentation assay, fluorescence‐activated cell sorting, colorimetric assay for caspases, and fluorescent probe for measurement of mitochondrial membrane potential were used to study the leishmanial lipid–induced apoptotic pathway in SFMCs.

Results

Leishmanial lipid inhibited the release of tumor necrosis factor α, interleukin‐1β, and NO in the culture, decreased their cytosolic protein levels, and decreased NF‐κB p65 levels in SFMCs, in a dose‐dependent manner. It had the reverse effect on interleukin‐10 levels. Leishmanial lipid–induced apoptosis involved the activation of caspase 3, caspase 9, and Bax, the release of cytochrome c, the alteration of mitochondrial membrane potential, and the down‐regulation of Bcl‐2.

Conclusion

These results suggest that leishmanial lipid has strong antiinflammatory and apoptosis‐inducing effects on SFMCs from patients with RA, and that apoptosis occurs via the mitochondrial pathway.
Neuroimaging findings in children with rare or novel de novo chromosomal anomalies
Authors: Epstein Leon G. , Jalali Ali , Chary Ajit N. , Khan Sophia , Ross Joshua , Coppinger Justine , Carlson Katrin , Charrow Joel , Burton Barbara , Zimmerman Donald , Curran John , Kim Francine , Nguyen Pam , Burrowes Delilah , Angle Brad , Stack Cynthia , Shaffer Lisa , Kessler John A. , Bassuk Alexander G.
Published: February 2008

BACKGROUND:

De novo constitutional chromosomal anomalies provide important insights into the genetic loci responsible for congenital neurological disorders. However, most phenotypic descriptions of patients with rare chromosomal abnormalities are published as individual case reports or small group studies, making genotype‐phenotype correlations unclear. Moreover, many clinical genetic reports do not include neuroimaging.

METHODS:

We conducted a retrospective case series study of all children who had genetic testing done at Children's Memorial Hospital in Chicago, Illinois between 1985 and 2006. The case series was selected from a database containing all chromosomal testing results, clinical data, and neuroimaging. Clinical examination results were assigned by board certified geneticists and/or neurologists and neuroimages were reviewed by both a neurologist or neuroradiologist and a blinded neurologist.

RESULTS:

Of the 28,108 children in the series, we identified 34 children with novel or apparently novel de novo chromosomal abnormalities. Several of the cases represent potentially new genetic loci for neurological malformations and novel syndromic conditions.

CONCLUSIONS:

This study demonstrates the utility of large clinical databases in assessing genotype‐phenotype correlations and mapping loci for congenital neurological disorders. We describe a case‐series strategy to analyze existing databases to reveal new genotype‐phenotype correlations. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.
Long‐term clinical outcomes after sirolimus‐eluting stent implantation for treatment of restenosis within bare‐metal versus drug‐eluting stents
Authors: Whan Lee Cheol , Kim Sang‐Hyun , Suh Jon , Park Duk‐Woo , Lee Seung‐Hwan , Kim Young‐Hak , Hong Myeong‐Ki , Kim Jae‐Joong , Park Seong‐Wook , Park Seung‐Jung
Published: March 2008

Background:

Sirolimus‐eluting stents have been increasingly used for treatment of restenosis after implantation of bare metal stents (BMSs) or drug‐eluting stents (DESs), but little is known regarding their long‐term outcomes.

Methods:

We compared long‐term clinical outcomes in 295 patients treated with sirolimus‐eluting stents for post‐BMS (n = 224) vs. post‐DES (n = 71) restenosis. All follow‐ups were at least 12 months, and the primary endpoint was major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction (MI) or target lesion revascularization (TLR).

Results:

Baseline characteristics were similar between the two groups, except that mean lesion length (28.0 ± 16.2 vs. 19.5 ± 13.6, P < 0.01) and mean stented length (35.4 ± 19.2 vs. 25.7 ± 14.7, P < 0.01) were significantly longer in the post‐BMS group. Major in‐hospital complications occurred in 2 patients. During a mean follow‐up of 31.3 ± 11.1 months, there were 9 deaths (4 cardiac, 5 noncardiac), 3 nonfatal MIs, and 25 TLRs. Late stent thrombosis was documented in 2 patients (1 in each group). There were no between group differences in cardiac or total deaths, but there were trends toward less frequent cardiac death/MI or TLR in the post‐BMS group. The cumulative probability of MACE‐free survival was significantly better for the post‐BMS group (95.0% ± 1.5% vs. 87.3% ± 4.0% at 1 year; 93.0% ± 1.7% vs. 81.0% ± 5.2% at 2 years; Log Rank P = 0.016). In multivariate analysis, post‐DES restenosis was the only significant predictor of MACE (OR 3.29, 95%CI 1.13–9.61, P = 0.029).

Conclusions:

Sirolimus‐eluting stents were effective for treatment of in‐stent restenosis, but post‐DES restenosis was associated with poorer outcomes than post‐BMS restenosis. © 2008 Wiley‐Liss, Inc.
ChemInform Abstract: Preparation of Magneto‐Resistive Sr2FeMoO6 Through Molybdic Acid Gelation.
Authors: Takeda Takashi , Ito Masahiro , Kikkawa Shinichi
Published: February 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Physicochemical Properties of the EuBr2—KBr Binary System.
Authors: Rycerz L. , Ingier‐Stocka E. , Cieslak‐Golonka M. , Wojciechowska A. , Gadzuric S. , Gaune‐Escard M.
Published: February 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Electrochemical Characterization of Layered Li(Ni1/3Co1/3Mn1/3)O2 Cathode Materials by Low‐Temperature Solid‐State Reaction.
Authors: Liu Jingjing , Qiu Weihua , Yu Lingyan , Zhao Hailei , Li Tao
Published: February 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Infinite‐Layer Iron Oxide with a Square‐Planar Coordination.
Authors: Tsujimoto Y. , Tassel C. , Hayashi N. , Watanabe T. , Kageyama H. , Yoshimura K. , Takano M. , Ceretti M. , Ritter C. , Paulus W.
Published: February 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Enantioselectivity of P‐Chiral Phosphine Ligands with Alkynyl Groups.
Authors: Imamoto Tsuneo , Saitoh Youichi , Koide Aya , Ogura Tomokazu , Yoshida Kazuhiro
Published: February 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.