bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma
Authors: Devitt Bianca , Liu Wendy , Salemi Renato , Wolfe Rory , Kelly John , Tzen Chin‐Yuan , Dobrovic Alexander , McArthur Grant 
Published: May 2011

SummaryThe effect of NRAS mutations on the pathological features and clinical outcomes in patients with cutaneous melanoma was compared with that of tumors containing BRAFV600E mutations and tumors wild type for both (WT). Clinical outcome data were obtained from a prospective cohort of 249 patients. Mutations involving NRAS and BRAFV600E were detected by PCR and were sequence verified. Cox proportional hazards regression was performed to relate NRAS and BRAF mutations to clinical outcome. Seventy‐five percentage of NRAS mutations occurred in tumors >1 mm thick (BRAFV600E 40%, WT 34%); 75% of NRAS mutations had >1 mitosis/mm2 (BRAFV600E 40%, WT 55%). When compared to WT, multivariate analysis of melanoma‐specific survival (MSS) identified NRAS mutations as an adverse prognostic factor [hazard ratio (HR) 2.96; P = 0.04] but not BRAFV600E mutations (HR 1.73; P = 0.23). NRAS mutations were associated with thicker tumors and higher rates of mitosis when compared to BRAFV600E and WT melanoma and independently of this, with shorter MSS.
Metabolic Antianginal Agent Ranolazine Offers Good Symptom Relief in a Patient with Inoperable Severe Aortic Stenosis
Authors: Athauda‐arachchi Pandula , Lang Chim 
Published: May 2011

SummarySevere inoperable aortic stenosis is a challenge for clinicians. Management of symptoms with traditional antianginal agents, which exert hemodynamic changes often may not be possible in such patient groups. We report the first known case of the safe use of Ranolazine with good symptomatic relief of angina in an 88‐year‐old lady with isolated severe aortic stenosis (without significant coronary disease) who was not suitable for surgical or percutaneous valve replacement due to medical comorbidity.
The Role of OATP1B1 and BCRP in Pharmacokinetics and DDI of Novel Statins
Authors: Hua Wen Jin , Hua Wei Xiao , Fang Hu Jin 
Published: May 2011

SUMMARYThe aim of this review is to provide useful information not only for studying the effect of OATP1B1 and/or BCRP gene mutation on pharmacokinetics of novle statins of pitavastatin and rosuvastatin but also for studying drug–drug interactions (DDI) between the novle statins and other substrates of OATP1B1 and/or BCRP. Intra‐ and inter‐ethnic differences in pharmacokinetic profiles of clinically relevant drugs are important issues reported in many papers not only for scenes of appropriate drug used in clinical settings but also for those of the drug development. Pharmacogenomics is extremely useful for understanding these racial differences. Recent pharmacogenetics study have disclosed important roles of drug transporters in the pharmacokinetic (PK) profiles of some clinically relevant drugs. In this presentation, we introduce single nucleotide polymorphisms (SNPs) of OATP1B1 and BCRP and review the contribution of genetic polymorphisms of the transporters to the pharmacokinetics of dual substrates as pitavastatin and rosuvastatin from recent study. At the same time, the DDIs between pitavastatin or rosuvastatin and other drug have been extensively concerned because of inhibiting OATP1B1‐mediated hepatic uptake or BCRP‐mediated hepatic efflux of pitavastatin and rosuvastatin. This review summarized the current studies about the role of OATP1B1 and BCRP in DDIs between pitavastatin or rosuvastatin and other clinically relevant drugs. The role of OATP1B1 and BCRP gene mutation can affect the PK profiles of pitavastatin and rosuvastatin. The DDIs between the novle statins and other substrates of OATP1B1 or BCRP may occur and cause change in the pharmacokinetic of the novle statins.
Artelon® Tissue Reinforcement in the Repair of a Ruptured, Degenerative Rotator Cuff in an Elderly Man
Authors: Zhaeentan Soheila , Hagert Elisabet 
Published: May 2011

Background Massive degenerative rotator cuff tears are a considerable problem in the elderly. It is known that about one third of surgical repairs of damaged rotator cuffs result in re-tear. The most common reason for this failure is poor quality of the cuff due to degenerative changes. The aim of our study was to see if Artelon Tissue Reinforcement® (ATR) in the repair of a degenerative rotator cuff tear could improve the postoperative outcome. Methods An 81-year old man was treated surgically with repair of a massive degenerative rotator cuff tear, reinforced by an ATR-patch. The patient was followed postoperatively with clinical examinations and MRI at 6- and 15-months postoperatively. Objective outcome measures using Constant Score, WORC and Oxford Shoulder Score were analyzed 2.5 years postoperatively. Results The MRI showed maintained integrity of the rotator cuff at both 6- and 15-months postoperatively. The results from WORC and Oxford Shoulder Score indicate a return to normal shoulder function. Discussion The experience from this case and two other similar cases with excellent patient satisfaction and no signs of adverse effects has encouraged us to commence a prospective, randomized study to further analyze the effect of ATR in treating degenerative rotator cuff tears.
The use of an Extended Humeral Head (CTA) Prosthesis in Patients Suffering with Rheumatoid Arthritis
Authors: Crawford Louise A. , Thompson Neville W. , Nuttall David , Haines John F. , Trail Ian , Birch Ann 
Published: May 2011

Background The results of shoulder replacement in patients suffering with rheumatoid arthritis, particularly in the presence of a massive cuff tear and glenoid erosion, are often unsatisfactory. Although patients can achieve satisfactory pain relief, movement and function are often limited. In the present study, we report the use of the extended head prosthesis in this group of patients. Methods Thirty-two patients (33 shoulders) underwent this procedure and were followed up for a mean of 4 years. Results At review, as well as showing a statistically significant diminution in pain, movements, particularly flexion and external rotation, were also significantly improved. In addition, the American Shoulder and Elbow Surgeons and Constant–Morley function scores had also improved. The overall survivalship at 8 years was 93%. Discussion We consider that these results are comparable if not better than a standard hemi-arthroplasty. In some cases, however, radiological follow-up has shown progressive subacromial and glenoid erosion. The significance of this remains unknown at present. Finally, in one patient, the humeral head subluxed anteriorly, resulting in revision to a reverse prosthesis.
Prevalence of Methicillin‐ResistantStaphylococcion a Farm: Staff can Harbour MRS When Animals Do Not
Authors: Aquino G. de V. , Maluta R. P. , de Ávila F. A. 
Published: May 2011

SummaryThe aim of this work was to establish the prevalence of methicillin‐resistantStaphylococci(MRS) in the animals and staff of a teaching and research farm. Samples of dairy cattle (36), beef cattle (26), sheep (19), horses (21), pigs (23), goats (23) and humans (13) were collected and screened for the presence of MRS. The detection ofmecA gene was performed by PCR to determine the resistance of the samples to methicillin. Antimicrobial‐resistance testing to penicillin, meropenem, ceftriaxone, cephalothin, oxacillin, levofloxacin, enrofloxacin, chloramphenicol, ciprofloxacin, gentamicin, clindamycin, erytromycin, linezolid, sulfamethoxazole/trimethoprim, tetracycline, doxycycline and vancomycin was performed on themecA+ isolates. From the 161 samples, four methicillin‐resistant coagulase‐negativeStaphylococci(MRCoNS) were isolated from human beings (31%), whereas none was isolated from animals (0%). No methicillin‐resistantStaphylococcus aureus(MRSA) were isolated. All of the MRCoNS isolates from this work presented different antimicrobial resistance patterns. MRCoNS may be present in humans associated with animals while not present in the animals. Selective pressure outside of the farm and a lack of MRCoNS transmission between humans and animals may be responsible for this lack of correlation.
The Prevalence and Genetic Diversity of Campylobacter spp. in Domestic ‘Backyard’ Poultry in Canterbury, New Zealand
Authors: Anderson J. , Horn B. J. , Gilpin B. J. 
Published: May 2011

SummaryCampylobacteriosis is the most commonly notified illness in New Zealand. Whilst the importance of commercial poultry in campylobacteriosis is well established, little is known about the possible role of chickens kept at home as a direct animal/faecal contact or consumption exposure pathway. The aim of this study was to determine the prevalence and genetic diversity of Campylobacter spp. in domestic backyard chicken flocks in the Canterbury region of New Zealand. Poultry faecal samples were collected from 35 domestic ‘backyard’ poultry flocks from urban and rural properties around the Canterbury Region of New Zealand. A total of 291 samples were collected and tested for the presence of thermotolerant Campylobacter spp. and positive isolates were analysed using pulsed‐field gel electrophoresis (PFGE) using both SmaI and KpnI enzymes. There was a high prevalence of Campylobacter spp. with 86% of flocks testing positive. Campylobacter jejuni alone, Campylobacter coli alone and both C. jejuni and C. coli were detected in 20 (57%), 2 (6%) and 8 (23%) of the flocks respectively. SmaI/KpnI PFGE analysis identified 50 different genotypes across the 35 flocks. Genotype diversity richness was highest on the lifestyle block and farm properties with 43 different genotypes isolated, whilst urban properties displayed the least richness with 12 genotypes isolated. Rural flocks tended to have more different genotypes in a given flock than urban flocks. Comparison of the genotypes with the PulseNet Aotearoa Campylobacter database showed that 28 of the genotypes had previously been isolated from human cases of campylobacteriosis. Many of these were also indistinguishable from Campylobacter spp. previously isolated from retail chicken. Therefore, contact with backyard poultry or their faecal material is a potential additional infection pathway outside of exposure to the established pathways associated with the consumption of Campylobacter‐contaminated commercial meat or foods cross‐contaminated from contaminated poultry.
Incubation of Whole Blood at 39°C Augments Gamma Interferon (IFN-γ)-Induced Protein 10 and IFN-γ Responses to Mycobacterium tuberculosis Antigens
Authors: Aabye Martine G. , Ravn Pernille , Johansen Isik S. , Eugen-Olsen Jesper , Ruhwald Morten 
Published: May 2011

ABSTRACT

A rarely challenged dogma in cell-mediated immune (CMI) assays is the incubation temperature, 37°C. Fever augments proinflammatory immune responses
in vivo
, and the aim of this study was to explore whether incubation at fever-range temperature could increase antigen-specific biomarker responses. We compared CMI responses following incubation of whole blood at 37°C and 39°C. Whole blood was obtained from (i) 34 healthy subjects whose blood was incubated with TB10.4 antigen, present in the
Mycobacterium bovis
bacillus Calmette-Guérin vaccine and many environmental mycobacteria; (ii) 8 TB patients and 8 controls incubated with
Mycobacterium tuberculosis
-specific antigens in the QuantiFERON-TB Gold test (QFT-IT); and (iii) from both groups incubated with a T cell mitogen. T cell responses (gamma interferon [IFN-γ]) and responses from antigen-presenting cells (IFN-γ-induced protein 10 [IP-10]) were determined. We further evaluated the effect of adding interleukin-7 (IL-7) and blocking IL-10 during incubation. In TB patients, IFN-γ and IP-10 levels were increased 4.1- and 3.4-fold, respectively, at 39°C incubation (
P
< 0.001). Similar results were seen after mitogen stimulation. In subjects responding to TB10.4, the effects were less pronounced and significant only for IP-10. Incubation at 39°C increased IP-10 and IFN-γ responsiveness to both antigens and mitogen in persons with baseline or initial low responses. Adding IL-7 and blocking IL-10 augmented the effects in synergy with fever-range temperature. Incubation at fever-range temperature vividly increases CMI responsiveness to antigen stimulation
in vitro
in tuberculosis patients and may increase the sensitivity of CMI assays.
Enoyl-Coenzyme A Hydratase and Antigen 85B of Mycobacterium habana Are Specifically Recognized by Antibodies in Sera from Leprosy Patients
Authors: Serafín-López J. , Talavera-Paulin M. , Amador-Molina J. C. , Alvarado-Riverón M. , Vilchis-Landeros M. M. , Méndez-Ortega P. , Fafutis-Morris M. , Paredes-Cervantes V. , López-Santiago R. , León C. I. , Guerrero M. I. , Ribas-Aparicio R. M. , Mendoza-Hernández G. , Carreño-Martínez C. , Estrada-Parra S. , Estrada-García I. 
Published: May 2011

ABSTRACTLeprosy is an infectious disease caused byMycobacterium leprae, which is a noncultivable bacterium. One of the principal goals of leprosy research is to develop serological tests that will allow identification and early treatment of leprosy patients.M. habanais a cultivable nonpathogenic mycobacterium and candidate vaccine for leprosy, and several antigens that cross-react betweenM. lepraeandM. habanahave been discovered. The aim of the present study was to extend the identification of cross-reactive antigens by identifyingM. habanaproteins that reacted by immunoblotting with antibodies in serum samples from leprosy patients but not with antibodies in sera from tuberculosis (TB) patients or healthy donors (HDs). A 28-kDa antigen that specifically reacted with sera from leprosy patients was identified. To further characterize this antigen, protein spots were aligned in two-dimensional polyacrylamide gels and Western blots. Spots cut out from the gels were then analyzed by mass spectrometry. Two proteins were identified: enoyl-coenzyme A hydratase (lipid metabolism; ML2498) and antigen 85B (Ag85B; mycolyltransferase; ML2028). These proteins represent promising candidates for the design of a reliable tool for the serodiagnosis of lepromatous leprosy, which is the most frequent form in Mexico.
Dengue Virus Immunoglobulin M Detection in a Reference Laboratory Setting during the 2010 Dengue Virus Outbreak on Caribbean Islands
Authors: Prince Harry E. , Matud Jose L. , Lieberman Jay M. 
Published: May 2011

ABSTRACTA large outbreak of dengue virus (DV) infections occurred on Caribbean islands during 2010, with cases peaking during the second half of the year. In conjunction with the outbreak, we observed an unprecedented spike in the number of sera submitted for DV antibody testing between June and December 2010, with a concomitant increase in the number of IgM-positive specimens, indicative of acute DV infection. Analysis of the place of residence of the IgM-positive patients identified from June to December of 2010 revealed that 58.1% were residents of Caribbean islands (Puerto Rico and the U.S. Virgin Islands), whereas 40.6% were residents of the U.S. mainland or Hawaii. The U.S. residents represented 42 states plus the District of Columbia, but most (53%) were from just 3 states (California, Florida, and New York). In comparison to the Caribbean IgM-positive patient group, the U.S. IgM-positive patient group contained proportionately more adults 21 to 60 years old and fewer individuals <21 years old. These findings indicate that the 2010 Caribbean DV outbreak affected many U.S. residents (mostly adults, presumably travelers) from diverse geographic areas and emphasize the potential for a viremic DV-infected returning traveler to spark a local DV outbreak by introducing DV into a community with competent mosquito vectors.
Comparative Study of the Standard Fluorescent Antibody to Membrane Antigen (FAMA) Assay and a Flow Cytometry-Adapted FAMA Assay To Assess Immunity to Varicella-Zoster Virus
Authors: Lafer M. M. , Weckx L. Y. , de Moraes-Pinto M. I. , Garretson A. , Steinberg S. P. , Gershon A. A. , LaRussa P. S. 
Published: May 2011

ABSTRACTA flow cytometry-adapted fluorescent antibody to membrane antigen (FAMA) assay to detect IgG antibodies against varicella-zoster virus (VZV) was developed and tested in 62 serum samples, showing 90.32% accuracy obtained from a receiver operating characteristic (ROC) curve with a 0.9125 (95% confidence interval [CI], 0.829 to 1.00) area below the curve compared to the result with standard FAMA.
Unusual Case of Resistance to Amphotericin B in Visceral Leishmaniasis in a Region in India Where Leishmaniasis Is Not Endemic
Authors: Srivastava Pankaj , Prajapati Vijay Kumar , Rai Madhukar , Sundar Shyam 
Published: May 2011

ABSTRACT

The case of a patient with visceral leishmaniasis showing inadequate response to amphotericin B from a region where leishmaniasis is not endemic is reported, with the
Leishmania donovani
isolate showing increased tolerance to amphotericin B
in vivo
. Four single nucleotide polymorphisms (SNPs) detected in the cysteine proteinase B gene resulted in changes to the deduced amino acid sequence: valine→alanine and arginine→leucine. Overexpression and underexpression of proteins were observed in the 65- to 80-kDa range and at 20 kDa, respectively.
Rapid Diagnosis of Extensively Drug-Resistant Tuberculosis by Use of a Reverse Line Blot Hybridization Assay
Authors: Ajbani Kanchan , Shetty Anjali , Mehta Ajita , Rodrigues Camilla 
Published: May 2011

ABSTRACT
Drug resistance in tuberculosis (TB) is a matter of grave concern for TB control programs, as there is currently no cure for some extensively drug-resistant (XDR) strains. There is concern that this resistance could transmit, stressing the need for additional control measures, rapid diagnostic methods, and newer drugs for treatment. We developed an in-house assay that can rapidly detect resistance to drugs involved in the definition of XDR-TB directly from smear-positive specimens. Two hundred fifteen phenotypically XDR-TB isolates and 50 pansusceptible isolates were analyzed using a reverse line blot hybridization (RLBH) assay. The assay was also successfully applied to 73 smear-positive clinical specimens. The RLBH assay exhibited good sensitivity for the detection of resistance to isoniazid (99%), rifampin (99%), fluoroquinolones (95.3%), and second-line aminoglycosides (94.8%). The results from application of this assay on direct smear-positive clinical specimens revealed 93% concordance with the phenotypic drug susceptibility test (DST) results for the above-mentioned drugs. The time to accurate DST results was significantly reduced from weeks to 3 days. This molecular assay is a highly accurate tool for screening for XDR-TB, which achieves a substantial reduction in diagnostic delays.
Role of Proteases in the Release of Porcine Epidemic Diarrhea Virus from Infected Cells
Authors: Shirato Kazuya , Matsuyama Shutoku , Ujike Makoto , Taguchi Fumihiro 
Published: May 2011

ABSTRACT
Porcine epidemic diarrhea virus (PEDV), a causative agent of pig diarrhea, requires a protease(s) for multicycle replication in cultured cells. However, the potential role of proteases in the infection process remains unclear. In order to explore this, we used two different approaches: we infected either Vero cells in the presence of trypsin or Vero cells that constitutively express the membrane-associated protease TMPRSS2 (Vero/TMPRSS2 cells). We found that PEDV infection was enhanced, and viruses were efficiently released into the culture fluid, from Vero cells infected in the presence of protease, while in cells without protease, the virus grew, but its release into the culture fluid was strongly hampered. Cell-to-cell fusion of PEDV-infected cells and cleavage of the spike (S) protein were observed in cells with protease. When infected Vero cells were cultured for 3 days in the absence of trypsin but were then treated transiently with trypsin, infectious viruses were immediately released from infected cells. In addition, treatment of infected Vero/TMPRSS2 cells with the protease inhibitor leupeptin strongly blocked the release of virus into the culture fluid. Under electron microscopy, PEDV-infected Vero cells, as well as PEDV-infected Vero/TMPRSS2 cells treated with leupeptin, retained huge clusters of virions on their surfaces, while such clusters were rarely seen in the presence of trypsin and the absence of leupeptin in Vero and Vero/TMPRSS2 cells, respectively. Thus, the present study indicates that proteases play an important role in the release of PEDV virions clustered on cells after replication occurs. This unique observation in coronavirus infection suggests that the actions of proteases are reminiscent of that of the influenza virus neuraminidase protein.
Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing Epitopes
Authors: McLellan Jason S. , Yang Yongping , Graham Barney S. , Kwong Peter D. 
Published: May 2011

ABSTRACT
Respiratory syncytial virus (RSV) invades host cells via a type I fusion (F) glycoprotein that undergoes dramatic structural rearrangements during the fusion process. Neutralizing monoclonal antibodies, such as 101F, palivizumab, and motavizumab, target two major antigenic sites on the RSV F glycoprotein. The structures of these sites as peptide complexes with motavizumab and 101F have been previously determined, but a structure for the trimeric RSV F glycoprotein ectodomain has remained elusive. To address this issue, we undertook structural and biophysical studies on stable ectodomain constructs. Here, we present the 2.8-Å crystal structure of the trimeric RSV F ectodomain in its postfusion conformation. The structure revealed that the 101F and motavizumab epitopes are present in the postfusion state and that their conformations are similar to those observed in the antibody-bound peptide structures. Both antibodies bound the postfusion F glycoprotein with high affinity in surface plasmon resonance experiments. Modeling of the antibodies bound to the F glycoprotein predicts that the 101F epitope is larger than the linear peptide and restricted to a single protomer in the trimer, whereas motavizumab likely contacts residues on two protomers, indicating a quaternary epitope. Mechanistically, these results suggest that 101F and motavizumab can bind to multiple conformations of the fusion glycoprotein and can neutralize late in the entry process. The structural preservation of neutralizing epitopes in the postfusion state suggests that this conformation can elicit neutralizing antibodies and serve as a useful vaccine antigen.
Architecture and Regulation of the HIV-1 Assembly and Holding Compartment in Macrophages
Authors: Welsch Sonja , Groot Fedde , Kräusslich Hans-Georg , Keppler Oliver T. , Sattentau Quentin J. 
Published: May 2011

ABSTRACT
Productive infection of macrophages is central to HIV-1 pathogenesis. Newly formed virions bud into a tubular membranous compartment that is contiguous with the plasma membrane. However, little is known about the structure of this compartment and its potential regulation by infection. Here we characterized this compartment in macrophages using electron tomography and electron microscopy with stereology. We found an intricate, interconnected membrane network that constitutes a preexisting physiologic structure in macrophages but which expands in size upon HIV-1 infection. Membranes required for this expansion were apparently derived from preexisting pools of plasma membrane. Physical connections between this compartment and the extracellular milieu were frequently made by tube-like structures of insufficient diameter for virion passage. We conclude that HIV-1 induces the expansion of a complex membranous labyrinth in macrophages in which the virus buds and can be retained, with potential consequences for transmission and immune evasion.