bluuebunny/crossref_metadata_2025_split huggingface dataset:
C4d‐negative antibody‐mediated rejection with high anti‐angiotensin II type I receptor antibodies in absence of donor‐specific antibodies
Authors: Fuss Alexander , Hope Christopher M , Deayton Susan , Bennett Greg Donald , Holdsworth Rhonda , Carroll Robert P , Coates P Toby H 
Published: February 2015

AbstractAimsAcute antibody‐mediated rejection can occur in absence of circulating donor‐specific antibodies. Agonistic antibodies targeting the anti‐angiotensin II type 1 receptor (anti‐AT1R) are emerging as important non‐human leucocyte antigen (HLA) antibodies. Elevated levels of anti‐angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure.MethodsWe report 11 cases of biopsy‐proven, Complement 4 fragment d (C4d)‐negative, acute rejection occurring without circulating donor‐specific anti‐HLA antibodies. In eight cases, anti‐angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti‐angiotensin receptor antibody screening.ResultsAll subjects fulfilled Banff 2013 criteria for antibody‐mediated rejection and all responded to anti‐rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy.ConclusionsThese cases support the routine assessment of anti‐AT1R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre‐emptive treatment with angiotensin receptor blockers.
Surgical Site Infection After Skin Excisions in Children: Is Field Sterility Sufficient?
Authors: Nuzzi Laura C. , Greene Arin K. , Meara John G. , Taghinia Amir , Labow Brian I. 
Published: February 2015

AbstractSkin excisions are common procedures in children. They may be performed in the clinic using field sterility or the operating room with strict sterile technique. We compared the effect of these locations and the use of antibiotics on the incidence of surgical site infection (SSI) after skin excisions. Patients ages 0–18 years presenting to our department for the excision of lesions from 2006 to 2010 with complete medical records were included in our study. Records were reviewed for demographic characteristics, presentation, perioperative conditions, and postoperative SSI and other wound complications. Analyses were performed to estimate the costs associated with sterility technique and perioperative antibiotic use. We identified 700 patients with a mean age of 9.1 years. Of 872 lesions excised, 0.3% resulted in SSI and 1.8% had other wound complications. The incidence of SSI did not vary according to sterility technique, antibiotic usage, surgeon, age, or lesion size, type, or location. The equipment costs to excise a lesion in the operating room were 200% greater than in the clinic. The incidence of SSI after excision of benign lesions in children did not differ between those performed using clinic field sterility and those using the standard aseptic sterile technique in the operating room. A considerable cost savings could be realized by adopting field sterility for simple excisions performed in the operating room and avoiding routine perioperative antibiotics in pediatric skin excisions.
Multicentric Reticulohistiocytosis: A Case Report of an Atypical Presentation in a 2‐Year‐Old
Authors: Olson Jaleh , Mann Julianne A. , White Kevin , Cartwright Victoria W. , Bauer Jeremy , Nolt Dawn 
Published: February 2015

AbstractMulticentric reticulohistiocytosis (MRH) is a rare systemic inflammatory granulomatous disease marked by severe and often rapidly progressive polyarticular arthritis and cutaneous papulonodules. Initial clinical diagnosis may be difficult. We describe a 2‐year‐old girl presenting with pink dermal papules on the forehead, thighs, elbows, knees, and palms of the hands. Based on clinical findings and skin biopsy results, she was initially diagnosed with granuloma annulare. At 5 years of age, she developed arthritis, fatigue, and more widespread skin papules leading to the diagnosis of MRH. To our knowledge, this is the youngest individual with MRH yet described. We outline the timeline and unique features of her case and review the literature pertaining to MRH in children. Although rare, MRH can be permanently debilitating, making prompt diagnosis critical. A standardized approach to investigation and management needs to be developed.
Endogenous Retinoic Acid Required to Maintain the Epidermis Following Ultraviolet Light Exposure in SKH‐1 Hairless Mice
Authors: Gressel Katherine L. , Duncan F. Jason , Oberyszyn Tatiana M. , La Perle Krista M. , Everts Helen B. 
Published: February 2015

AbstractUltraviolet light B (UVB) exposure induces cutaneous squamous cell carcinoma (cSCC), one of the most prevalent human cancers. Reoccurrence of cSCC in high‐risk patients is prevented by oral retinoids. But oral retinoid treatment causes significant side effects; and patients develop retinoid resistance. Exactly how retinoids prevent UVB‐induced cSCC is currently not well understood. Retinoid resistance blocks mechanistic studies in the leading mouse model of cSCC, the UVB‐exposed SKH‐1 hairless mouse. To begin to understand the role of retinoids in UVB‐induced cSCC we first examined the localization pattern of key retinoid metabolism proteins by immunohistochemistry 48 h after UVB treatment of female SKH‐1 mice. We next inhibited retinoic acid (RA) synthesis immediately after UVB exposure. Acute UVB increased RA synthesis, signaling and degradation proteins in the stratum granulosum. Some of these proteins changed their localization; while other proteins just increased in intensity. In contrast, acute UVB reduced the retinoid storage protein lectin:retinol acyltransferase (LRAT) in the epidermis. Inhibiting RA synthesis disrupted the epidermis and impaired differentiation. These data suggest that repair of the epidermis after acute UVB exposure requires endogenous RA synthesis.
Hematologic and biochemical reference intervals for adult Friesian horses from North America
Authors: Sample Saundra H. , Fox Katherine M. , Wunn Denise , Roth Elizabeth , Friedrichs Kristen R. 
Published: February 2015

BackgroundEstablished breed‐specific reference intervals (RI) are an important tool for monitoring the health of horses. There is a lack of published work on breed‐specific RI for Friesian horses.ObjectivesThe goal of this project was to determine hematologic and biochemical RI for Friesian horses residing in North America.MethodsStrict inclusion and exclusion criteria were established for selection of reference subjects and for blood specimen collection and handling. Blood samples from 123 healthy, adult (range 3–18 years, median 8 years) Friesian horses of both sexes (70 mares, 45 geldings, and 8 stallions) were used to determine RI. Complete blood counts (CBC) and biochemistry profiles were performed on the Sysmex XT‐2000iV hematology and Olympus AU400 biochemistry analyzers, respectively, at IDEXX Laboratories Inc. (Columbus, OH, USA). Results were analyzed using Reference Value Advisor. According to the guidelines of the ASVCP, nonparametric RI with 90% confidence intervals were determined.ResultsIDEXX equine RI are transferrable to Friesian horses for 30 of 36 analytes. Friesian‐specific RI (medians) are recommended for the following variables: RBC 5.02–8.74 × 106/μL (6.66), HCT 27–42% (34), HGB 9.0–14.3 g/dL (11.4), lactate dehydrogenase 299–866 U/L (493), direct bilirubin 0.3–0.7 mg/dL (0.5), and anion gap 7–18 mEq/L (12).ConclusionsThe RI established in this study provide a useful baseline for the assessment of hematologic and biochemical data in Friesian horses residing in North America.
Review: Innate immunity, lipid metabolism and nutrition in canine atopic dermatitis
Authors: Pucheu‐Haston Cherie M. , Santoro Domenico , Bizikova Petra , Eisenschenk Melissa N. C. , Marsella Rosanna , Nuttall Tim 
Published: February 2015

BackgroundThe pathogenesis of canine atopic dermatitis (AD) involves dysfunction of the adaptive immune system. Recent evidence suggests that nonantigen‐specific inflammatory elements may play a role in the development and perpetuation of canineAD.ObjectivesThe objective of this review is to provide an update on recent advances in the understanding of the role of innate immune cells, keratinocytes, lipid metabolism and nutrition in the pathogenesis ofADin dogs.MethodsCitation databases, abstracts and proceedings from international meetings published between 2001 and 2013 are reviewed in this update. Where necessary, older articles are included for background information.ResultsMembers of the innate immune system (including dendritic cells, Langerhans cells and mast cells) and keratinocytes interact with each other and with environmental antigens during both induction and effector phases of atopic inflammation. The responses of these cells and associated noncellular factors (such as complement and protease‐activated receptors) to environmental stimuli influence the entire future course of the immune response to a given agent. Abnormalities in lipid metabolism may also influence the pathogenesis of canineADvia the production of inflammatory mediators and by alteration of epidermal barrier function and antigen presentation. However, a lack of fully controlled studies precludes definitive interpretation of these data.Conclusions and clinical importanceEvidence indicates that the cells and noncellular components of the innate immune system and the epidermis may play critical roles during both the sensitization and the effector phases of canineAD. Derangements in lipid metabolism may be involved in the pathogenesis ofADin dogs, but additional controlled studies are required in this area.
Induction of PERV antigen in porcine peripheral blood mononuclear cells by human herpesvirus 1
Authors: Kim Jiyeon , Kim Jung Heon , Hwang Eung Soo 
Published: February 2015

AbstractBackgroundXenotransplantation represents one of alternative candidates for allotransplantation due to the chronic shortage of suitable human tissues; however, many obstacles remain. Expression and release of endogenous retroviral antigens by porcine cells after transplantation may evoke adverse immune responses in human subjects. Here, we examined whether human herpesvirus 1 (HHV‐1) could induce the production of porcine endogenous retrovirus (PERV) antigens in porcine peripheral blood mononuclear cells (PBMCs).MethodsPorcine PBMCs were infected with HHV‐1 and examined for the production of PERV Gag protein and HHV‐1 using antigen‐capture ELISA and quantitative real‐time polymerase chain reaction (PCR), respectively.ResultsHHV‐1 infection resulted in a 1.7‐ to 33.2‐fold induction of PERV Gag relative to mock infection controls, compared to a 2.9‐ to 12.9‐fold induction following treatment with PMA. Expression of PERV Gag was detected in porcine PBMCs and PK‐15 cells after HHV‐1 infection by double immunofluorescence staining of PERV Gag and HHV‐1 antigen. The viability of HHV‐1‐infected porcine PBMCs was significantly lower than that of mock‐infected cells. The HHV‐1 level in the culture supernatant increased 5.2‐fold relative to controls 24‐h post‐infection, indicative of active replication within these cells; decreased levels of HHV‐1 were detected 72‐h post‐infection.ConclusionsThese results suggest that HHV‐1 may be capable of infecting transplanted porcine cells, resulting in strong direct induction of PERV antigen.
Pharmacodynamics of Amphotericin B Deoxycholate, Amphotericin B Lipid Complex, and Liposomal Amphotericin B against Aspergillus fumigatus
Authors: Al-Nakeeb Zaid , Petraitis Vidmantas , Goodwin Joanne , Petraitiene Ruta , Walsh Thomas J. , Hope William W. 
Published: February 2015

ABSTRACT

Amphotericin B is a first-line agent for the treatment of invasive aspergillosis. However, relatively little is known about the pharmacodynamics of amphotericin B for invasive pulmonary aspergillosis. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAMB), amphotericin B lipid complex (ABLC), and liposomal amphotericin B (LAMB) by using a neutropenic-rabbit model of invasive pulmonary aspergillosis. The study endpoints were lung weight, infarct score, and levels of circulating galactomannan and (1→3)-β-
d
-glucan. Mathematical models were used to describe PK-PD relationships. The experimental findings were bridged to humans by Monte Carlo simulation. Each amphotericin B formulation induced a dose-dependent decline in study endpoints. Near-maximal antifungal activity was evident with DAMB at 1 mg/kg/day and ABLC and LAMB at 5 mg/kg/day. The bridging study suggested that the “average” patient receiving LAMB at 3 mg/kg/day was predicted to have complete suppression of galactomannan and (1→3)-β-
d
-glucan levels, but 20 to 30% of the patients still had a galactomannan index of >1 and (1→3)-β-
d
-glucan levels of >60 pg/ml. All formulations of amphotericin B induce a dose-dependent reduction in markers of lung injury and circulating fungus-related biomarkers. A clinical dosage of liposomal amphotericin B of 3 mg/kg/day is predicted to cause complete suppression of galactomannan and (1→3)-β-
d
-glucan levels in the majority of patients.
Bestatin Induces Specific Changes in Trypanosoma cruzi Dipeptide Pool
Authors: Trochine Andrea , Creek Darren J. , Faral-Tello Paula , Barrett Michael P. , Robello Carlos 
Published: February 2015

ABSTRACT

Proteases and peptidases in
Trypanosoma cruzi
are considered potential targets for antichagasic chemotherapy. We monitored changes in low-mass metabolites in
T. cruzi
epimastigotes treated with bestatin, a dipeptide metalloaminopeptidase inhibitor. After treatment, multiple dipeptides were shown to be increased, confirming
in situ
inhibition of the leucine aminopeptidase of
T. cruzi
(LAPTc) and probably other peptidases.
Persistence of Vancomycin Resistance in Multiple Clones of Enterococcus faecium Isolated from Danish Broilers 15 Years after the Ban of Avoparcin
Authors: Bortolaia Valeria , Mander Manuela , Jensen Lars B. , Olsen John E. , Guardabassi Luca 
Published: February 2015

ABSTRACT

The occurrence and diversity of vancomycin-resistant
Enterococcus faecium
(VREF) were investigated in 100 Danish broiler flocks 15 years after the avoparcin ban. VREF occurred in 47 flocks at low fecal concentrations detectable only by selective enrichment. Vancomycin resistance was prevalently associated with a transferable nontypeable plasmid lineage occurring in multiple
E. faecium
clones. Coselection of sequence type 842 by tetracycline use only partly explained the persistence of vancomycin resistance in the absence of detectable plasmid coresistance and toxin-antitoxin systems.
phoU
Inactivation in Pseudomonas aeruginosa Enhances Accumulation of ppGpp and Polyphosphate
Authors: de Almeida Luiz Gustavo , Ortiz Julia Helena , Schneider René P. , Spira Beny 
Published: February 2015

ABSTRACT

Inorganic polyphosphate (polyP) is a linear polymer composed of several molecules of orthophosphate (P
i
) linked by energy-rich phosphoanhydride bonds. In
Pseudomonas aeruginosa
, P
i
is taken up by the ABC transporter Pst, encoded by an operon consisting of five genes. The first four genes encode proteins involved in the transport of P
i
and the last gene of the operon,
phoU
, codes for a protein which exact function is unknown. We show here that the inactivation of
phoU
in
P. aeruginosa
enhanced P
i
removal from the medium and polyP accumulation. The
phoU
mutant also accumulated high levels of the alarmone guanosine tetraphosphate (ppGpp), which in turn increased the buildup of polyP. In addition,
phoU
inactivation had several pleiotropic effects, such as reduced growth rate and yield and increased sensitivity to antibiotics and stresses. However, biofilm formation was not affected by the
phoU
mutation.
A Patatin-Like Protein Associated with the Polyhydroxyalkanoate (PHA) Granules of Haloferax mediterranei Acts as an Efficient Depolymerase in the Degradation of Native PHA
Authors: Liu Guiming , Hou Jing , Cai Shuangfeng , Zhao Dahe , Cai Lei , Han Jing , Zhou Jian , Xiang Hua 
Published: February 2015

ABSTRACT

The key enzymes and pathways involved in polyhydroxyalkanoate (PHA) biosynthesis in haloarchaea have been identified in recent years, but the haloarchaeal enzymes for PHA degradation remain unknown. In this study, a patatin-like PHA depolymerase, PhaZh1, was determined to be located on the PHA granules in the haloarchaeon
Haloferax mediterranei
. PhaZh1 hydrolyzed the native PHA (nPHA) [including native polyhydroxybutyrate (nPHB) and native poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (nPHBV) in this study] granules
in vitro
with 3-hydroxybutyrate (3HB) monomer as the primary product. The site-directed mutagenesis of PhaZh1 indicated that Gly
16
, Ser
47
(in a classical lipase box, G-X-S
47
-X-G), and Asp
195
of this depolymerase were essential for its activity in nPHA granule hydrolysis. Notably,
phaZh1
and
bdhA
(encoding putative 3HB dehydrogenase) form a gene cluster (
HFX_6463
to
_6464
) in
H. mediterranei
. The 3HB monomer generated from nPHA degradation by PhaZh1 could be further converted into acetoacetate by BdhA, indicating that PhaZh1-BdhA may constitute the first part of a PHA degradation pathway
in vivo
. Interestingly, although PhaZh1 showed efficient activity and was most likely the key enzyme in nPHA granule hydrolysis
in vitro
, the knockout of
phaZh1
had no significant effect on the intracellular PHA mobilization, implying the existence of an alternative PHA mobilization pathway(s) that functions effectively within the cells of
H. mediterranei
. Therefore, identification of this patatin-like depolymerase of haloarchaea may provide a new strategy for producing the high-value-added chiral compound (
R
)-3HB and may also shed light on the PHA mobilization in haloarchaea.
Human Infections with Sarcocystis Species
Authors: Fayer Ronald , Esposito Douglas H. , Dubey Jitender P. 
Published: February 2015

SUMMARY

Recurrent outbreaks of muscular sarcocystosis among tourists visiting islands in Malaysia have focused international attention on sarcocystosis, a disease once considered rare in humans.
Sarcocystis
species require two hosts, definitive and intermediate, to complete their life cycle. Humans can serve as definitive hosts, with intestinal sarcocystosis for two species acquired from eating undercooked meat:
Sarcocystis hominis
, from beef, and
Sarcocystis suihominis
, from pork. Symptoms such as nausea, stomachache, and diarrhea vary widely depending on the number of cysts ingested but appear more severe with pork than with beef. Humans serve as intermediate hosts for
Sarcocystis nesbitti
, a species with a reptilian definitive host, and possibly other unidentified species, acquired by ingesting sporocysts from feces-contaminated food or water and the environment; infections have an early phase of development in vascular endothelium, with illness that is difficult to diagnose; clinical signs include fever, headache, and myalgia. Subsequent development of intramuscular cysts is characterized by myositis. Presumptive diagnosis based on travel history to tropical regions, elevated serum enzyme levels, and eosinophilia is confirmed by finding sarcocysts in muscle biopsy specimens. There is no vaccine or confirmed effective antiparasitic drug for muscular sarcocystosis, but anti-inflammatory drugs may reduce symptoms. Prevention strategies are also discussed.
Coinfection with Blood-Stage Plasmodium Promotes Systemic Type I Interferon Production during Pneumovirus Infection but Impairs Inflammation and Viral Control in the Lung
Authors: Edwards Chelsea L. , Zhang Vivian , Werder Rhiannon B. , Best Shannon E. , Sebina Ismail , James Kylie R. , Faleiro Rebecca J. , de Labastida Rivera Fabian , Amante Fiona H. , Engwerda Christian R. , Phipps Simon , Haque Ashraful 
Published: February 2015

ABSTRACTAcute lower respiratory tract infections (ALRTI) are the leading cause of global childhood mortality, with human respiratory syncytial virus (hRSV) being a major cause of viral ALRTI in young children worldwide. In sub-Saharan Africa, many young children experience severe illnesses due to hRSV orPlasmodiuminfection. Although the incidence of malaria in this region has decreased in recent years, there remains a significant opportunity for coinfection. Recent data show that febrile young children infected withPlasmodiumare often concurrently infected with respiratory viral pathogens but are less likely to suffer from pneumonia than are non-Plasmodium-infected children. Here, we hypothesized that blood-stagePlasmodiuminfection modulates pulmonary inflammatory responses to a viral pathogen but does not aid its control in the lung. To test this, we established a novel coinfection model in which mice were simultaneously infected with pneumovirus of mice (PVM) (to model hRSV) and blood-stagePlasmodium chabaudi chabaudiAS (PcAS) parasites. We found thatPcAS infection was unaffected by coinfection with PVM. In contrast, PVM-associated weight loss, pulmonary cytokine responses, and immune cell recruitment to the airways were substantially reduced by coinfection withPcAS. Importantly,PcAS coinfection facilitated greater viral dissemination throughout the lung. AlthoughPlasmodiumcoinfection induced low levels of systemic interleukin-10 (IL-10), this regulatory cytokine played no role in the modulation of lung inflammation or viral dissemination. Instead, we found thatPlasmodiumcoinfection drove an early systemic beta interferon (IFN-β) response. Therefore, we propose that blood-stagePlasmodiumcoinfection may exacerbate viral dissemination and impair inflammation in the lung by dysregulating type I IFN-dependent responses to respiratory viruses.
MrSkn7 Controls Sporulation, Cell Wall Integrity, Autolysis, and Virulence in Metarhizium robertsii
Authors: Shang Yanfang , Chen Peilin , Chen Yixiong , Lu Yuzhen , Wang Chengshu 
Published: February 2015

ABSTRACT

Two-component signaling pathways generally include sensor histidine kinases and response regulators. We identified an ortholog of the response regulator protein Skn7 in the insect-pathogenic fungus
Metarhizium robertsii
, which we named MrSkn7. Gene deletion assays and functional characterizations indicated that MrSkn7 functions as a transcription factor. The
MrSkn7
null mutant of
M. robertsii
lost the ability to sporulate and had defects in cell wall biosynthesis but was not sensitive to oxidative and osmotic stresses compared to the wild type. However, the mutant was able to produce spores under salt stress. Insect bioassays using these spores showed that the virulence of the mutant was significantly impaired compared to that of the wild type due to the failures to form the infection structure appressorium and evade host immunity. In particular, deletion of
MrSkn7
triggered cell autolysis with typical features such as cell vacuolization, downregulation of repressor genes, and upregulation of autolysis-related genes such as extracellular chitinases and proteases. Promoter binding assays confirmed that MrSkn7 could directly or indirectly control different putative target genes. Taken together, the results of this study help us understand the functional divergence of Skn7 orthologs as well as the mechanisms underlying the development and control of virulence in insect-pathogenic fungi.