bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Engineered R-Type Pyocin Is a Highly Specific and Sensitive Bactericidal Agent for the Food-Borne Pathogen
Escherichia coli
O157:H7
Authors: Scholl Dean , Cooley Mike , Williams Steve R. , Gebhart Dana , Martin David , Bates Anna , Mandrell Robert 
Published: April 2009

ABSTRACT

Some strains of
Pseudomonas aeruginosa
produce R-type pyocins, which are high-molecular-weight phage tail-like protein complexes that have bactericidal activity against other
Pseudomonas
strains. These particles recognize and bind to bacterial surface structures via tail fibers, their primary spectrum determinant. R-type pyocins kill the cell by contracting a sheath-like structure and inserting their hollow core through the cell envelope, resulting in dissipation of the cellular membrane potential. We have retargeted an R-type pyocin to
Escherichia coli
O157:H7 by fusing a tail spike protein from an O157-specific phage, φV10, to the pyocin tail fiber. The φV10 tail spike protein recognizes and degrades the O157 lipopolysaccharide. This engineered pyocin, termed AVR2-V10, is sensitive and specific, killing 100% of diverse
E. coli
O157:H7 isolates but no other serotypes tested. AVR2-V10 can kill
E. coli
O157:H7 on beef surfaces, making it a candidate agent for the elimination of this pathogen from food products. All rare AVR2-V10-resistant mutants isolated and examined have lost the ability to produce the O157 antigen and are expected to have compromised virulence. In addition,
E. coli
O157:H7 exposed to and killed by AVR2-V10 do not release Shiga toxin, as is often the case with many antibiotics, suggesting potential therapeutic applications. The demonstration that a novel R-type pyocin can be created in the laboratory by fusing a catalytic tail spike from the family
Podoviridae
to a tail fiber of a member of the family
Myoviridae
is evidence that the plasticity observed among bacteriophage tail genes can, with modern molecular techniques, be exploited to produce nonnatural, targeted antimicrobial agents.
A Fusion Protein Vaccine Containing OprF Epitope 8, OprI, and Type A and B Flagellins Promotes Enhanced Clearance of Nonmucoid
Pseudomonas aeruginosa
Authors: Weimer Eric T. , Lu Haiping , Kock Nancy D. , Wozniak Daniel J. , Mizel Steven B. 
Published: April 2009

ABSTRACT

Although chronic
Pseudomonas aeruginosa
infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients, there is no approved vaccine for human use against
P. aeruginosa
. The goal of this study was to establish whether a multivalent vaccine containing
P. aeruginosa
type A and B flagellins as well as the outer membrane proteins OprF and OprI would promote enhanced clearance of
P. aeruginosa
. Intramuscular immunization with flagellins and OprI (separate) or OprI-flagellin fusion proteins generated significant antiflagellin immunoglobulin G (IgG) responses. However, only the fusions of OprI with type A and type B flagellins generated OprI-specific IgG. Immunization with a combination of OprF epitope 8 (OprF
311-341
), OprI, and flagellins elicited high-affinity IgG antibodies specific to flagellins, OprI, and OprF that individually promoted extensive deposition of C3 on
P. aeruginosa
. Although these antibodies exhibited potent antibody-dependent complement-mediated killing of nonmucoid bacteria, they were significantly less effective with mucoid isolates. Mice immunized with the OprF
311-341
-OprI-flagellin fusion had a significantly lower bacterial burden three days postchallenge and cleared the infection significantly faster than control mice. In addition, mice immunized with the OprF
311-341
-OprI-flagellin fusion had significantly less inflammation and lung damage throughout the infection than OprF-OprI-immunized mice. Based on our results, OprF
311-341
-OprI-flagellin fusion proteins have substantial potential as components of a vaccine against nonmucoid
P. aeruginosa
, which appears to be the phenotype of the bacterium that initially colonizes CF patients.
Identification ofmigR, a Regulatory Element of theFrancisella tularensisLive Vaccine StrainiglABCDVirulence Operon Required for Normal Replication and Trafficking in Macrophages
Authors: Buchan Blake W. , McCaffrey Ramona L. , Lindemann Stephen R. , Allen Lee-Ann H. , Jones Bradley D. 
Published: April 2009

ABSTRACTFrancisella tularensis, the etiological agent of tularemia, is capable of infecting a wide range of animals and causes a severe, lethal disease in humans. The pathogen evades killing by cells of the innate immune system utilizing genes encoding a pathogenicity island, includingiglABCD, and instead utilizes these cells as a niche for replication and dissemination to other organs within the host. Regulators of theiglgenes (e.g., MglA, SspA, FevR and PmrA) have been identified, but environmental stimuli and mechanisms of regulation are as yet unknown and are likely to involve additional gene products. In this work, we more closely examine the roles that environmental iron and the ferric uptake repressor protein (Fur) play in the regulation of theiglABCDoperon. We also used a genetic approach to identify and characterize a new regulator of theigloperon, designatedmigR(macrophageintracellulargrowthregulator; FTL_1542). Quantitative real-time reverse transcription-PCR in a site-directedmigRmutant confirmed the reduction in the number ofiglCtranscripts in this strain and also demonstrated reduced expression offevR. Comparison of themigRandfevRmutants in monocyte-derived macrophages (MDMs) and epithelial cell lines revealed a reduced ability for each mutant to grow in MDMs, yet only thefevRmutant exhibited impaired replication in epithelial cell lines. Confocal analysis of infected MDMs revealed that although neither mutant reached the MDM cytosol, thefevRmutant was trapped in lamp-1-positive phagosomes, whereas themigRmutant resided in mature phagolysosomes enriched with both lamp-1 and cathepsin D. Disruption ofmigRandfevRalso impaired the ability ofF. tularensisto prevent neutrophil oxidant production. Thus, we have identifiedmigR, a gene that regulates expression of theiglABCDoperon and is essential for bacterial growth in MDMs and also contributes to the blockade of neutrophil NADPH oxidase activity.
Secreted Dipeptidyl Peptidase IV Activity in the Dimorphic Fungal PathogenHistoplasma capsulatum
Authors: Cooper Kendal G. , Woods Jon P. 
Published: April 2009

ABSTRACTDipeptidyl peptidase type IV (DppIV) enzymes are broadly distributed phylogenetically and display diverse functions, including intercellular signaling, immunomodulation, protein maturation and processing, metabolism, and nutrient acquisition. We identified a secreted proteolytic activity inHistoplasma capsulatumeffective toward DppIV-specific substrates. In order to determine the gene(s) that encodes this activity, we identified two putativeDPPIVhomologs (HcDPPIVAandHcDPPIVB) inH. capsulatumbased on a homology search withAspergillus fumigatusDppIV. Comparative sequence analysis revealed that HcDppIVA is similar to secreted DppIV enzymes, while HcDppIVB clusters with intracellular DapB-like enzymes. Unexpectedly, silencing ofHcDPPIVAby RNA interference (RNAi) had no effect on secreted DppIV activity and anHcDPPIVA-null deletion mutant also showed no abrogation of secreted DppIV activity. In contrast, RNAi silencing ofHcDPPIVBsignificantly reduced the level of secreted DppIV activity. RNAi silencing ofHcDPPIVBin theHcDPPIVA-null mutant had no additional effect on secreted DppIV activity, indicating thatHcDPPIVAdoes not contribute to secreted activity. RNAi silencing ofHcDPPIVBdid not affect the ability to kill a murine macrophage-like cell line, RAW 264.7, indicating that this gene is not required for infection of macrophages.
Protection ofMycobacterium tuberculosisfrom Reactive Oxygen Species Conferred by themel2Locus Impacts Persistence and Dissemination
Authors: Cirillo Suat L. G. , Subbian Selvakumar , Chen Bing , Weisbrod Torin R. , Jacobs William R. , Cirillo Jeffrey D. 
Published: April 2009

ABSTRACTPersistence ofMycobacterium tuberculosisin humans represents a major roadblock to elimination of tuberculosis. We describe identification of a locus inM. tuberculosis, mel2, that displays similarity to bacterial bioluminescent loci and plays an important role during persistence in mice. We constructed a deletion of themel2locus and found that the mutant displays increased susceptibility to reactive oxygen species (ROS). Upon infection of mice by aerosol the mutant grows normally until the persistent stage, where it does not persist as well as wild type. Histopathological analyses show that infection with themel2mutant results in reduced pathology and both CFU and histopathology indicate that dissemination of themel2mutant to the spleen is delayed. These data along with growth in activated macrophages and infection of Phox−/−and iNOS−/−mice and bone marrow-derived macrophages suggest that the primary mechanism by whichmel2affects pathogenesis is through its ability to confer resistance to ROS. These studies provide the first insight into the mechanism of action for this novel class of genes that are related to bioluminescence genes. The role ofmel2in resistance to ROS is important for persistence and dissemination ofM. tuberculosisand suggests that homologues in other bacterial species are likely to play a role in pathogenesis.
Galactorrhoea following Acupuncture
Authors: Jenner Chris , Filshie Jacqueline 
Published: April 2009

A 41-year-old woman with breast cancer was referred to the pain management clinic for a course of acupuncture for intense pain following a subcutaneous mastectomy and a latissimus dorsi flap reconstruction. She was treated with a standard course of acupuncture for breast pain, using paravertebral segmental points, trigger points, plus contralateral LI4 on the non-lymphoedematous arm. She experienced an episode of galactorrhoea six days following the first treatment and during the second treatment. She had not previously lactated for four years. CT and MRI of the brain revealed no focal abnormality. Acupuncture has been used in to promote lactation in the Traditional Chinese literature using the ‘Tianzong’ acupoint SI11. This acupoint coincided with a trigger point over infraspinatus that was included in the neurophysiologically based acupuncture treatment. Quantitative analysis has shown an increase in the production of prolactin and oxytocin following acupuncture. These hormones are involved in the synthesis and release of milk from mammary glands respectively. This is the first report of galactorrhoea, in the contralateral normal breast, following acupuncture in a patient with breast cancer.
Does Acupuncture Contribute to the Treatment of Chronic Shoulder Pain (Csp)
Authors: Molsberger AF 
Published: April 2009

Objective Response of Chinese acupuncture compared to conservative orthopaedic treatment and unspecific needling in pain treatment on CSP. Design Prospective, randomized controlled trial with three blinded parallel groups; follow up three months. Setting Outpatients of 26 orthopaedists, who have attended a 140 hours training course on acupuncture. Patients Four hundred and twenty seven out-patients with a history of CSP ≥ six weeks, VAS ≥ 50 mm were selected; three random groups, six weeks treatment. 308 patients reported after three months follow up. Two strata: age 25–45 and age 46–65. Interventions Group 1: VAP: 15 treatments of verum acupuncture (VAP). Group 2: SHM: 15 treatments of non-specific needling, sham acupuncture (SHM). Group 3: COT: conventional conservative orthopaedic treatment (COT). Patients were blinded to allocation between verum and sham acupuncture. Main Outcome Measures Primary endpoint: pain reduction ≥ 50% on VAS three months after the end of the treatment protocol. Secondary endpoints: global assessments on a 4-score scale directly after the end of the treatment protocol. Results The results after three months follow up are: Highly significant effect of CAP over SHM and COT in the whole sample (P<0.0001) and in Stratum1 (P<0.001) and Stratum2 (P<0.001). Conclusions Acupuncture is an important supplement in the management of CSP. BMBF grant: 01KT9411/9
Neurogenic Pruritus: Treatment by Acupuncture
Authors: Stellon AJ 
Published: April 2009

Introduction Notalgia paraesthetica is a condition associated with itching, and unassociated with a rash, that affects a segment of the body innervated by T2-T6 dorsal spinal nerves. It is believed to be a type of neuropathy. This single-handed practice reports one such case. It also describes a further eight cases of “neurogenic” pruritus which share similar characteristics to this condition but are in segments of the body innervated by cervical and lumbar spinal nerves. Traditional acupuncture has been described to help with skin conditions and this study was performed to see if it was successful in this type of pruritus. Patients and Methods Over a nine-year period in a practice with an average list size of 2000 patients, nine patients aged 41 to 79 years presenting with segmental itching were identified. Other causes of pruritus were excluded by clinical examination, as well as by haematological and biochemical tests. Drug induced causes were also excluded. Duration of pruritus was six weeks (range 4 – 52 weeks). In eight patients itching was restricted to dermatomes innervated by the spinal nerves of the cervical spine, in two by the dorsal spine and in two by the lumbar spine. In three patients pruritus occurred in dermatomes innervated by two separate areas of the spine. Clinical examination revealed restricted cervical or lumbar movements in seven patients. Paravertebral tenderness and/or spasm of the paravertebral muscles was found in the areas of pruritus in seven patients. Skin changes associated with sympathetic nerve over-activity were noted in five patients. Six of the nine patients had x-ray evidence of degeneration of the spine. Results All nine patients were treated by deep intramuscular stimulation of the paravertebral muscles in the dermatomes affected by pruritus. In total a median of three treatments (range 2 – 5) was required to resolve the pruritus. Recurrence of symptoms occurred in four patients within 8 to 12 months of their last treatment over a period of follow-up of 0.5 – 9 years (median one year). Repeat acupuncture treatment resolved the pruritus. Discussion The term neurogenic pruritus describes and encompasses all conditions associated with segmental itching unassociated with a rash. The clinical signs of this condition are suggestive of an early neuropathy as a result of a degenerative condition of the spine. This is the first report of symptoms of such a condition being treated successfully by acupuncture.
Interventions to reduce the frequency of exacerbations of chronic obstructive pulmonary disease
Authors: Black P N , McDonald C F 
Published: April 2009

Abstract
Frequent exacerbations of chronic obstructive pulmonary disease (COPD) are associated with impaired quality of life, and hospital admissions for exacerbations account for a large proportion of the expenditure of COPD. An important objective when treating COPD is to reduce the frequency of exacerbations. Studies published in the last few years have increased our knowledge on how to prevent exacerbations, but a number of questions remain unanswered. Tiotropium, inhaled steroids and long-acting inhaled β agonists reduce the frequency of exacerbations, but further studies are necessary to determine if combining tiotropium with the other inhaled medicines is more effective than using them separately. There is evidence that mucolytics and prophylactic antibiotics reduce exacerbations, but there is uncertainty how these treatments should be used. Both influenza and pneumococcal vaccination are recommended in guidelines, although evidence for the latter remains controversial. Other interventions including oral bacterial extracts and self-management programmes warrant further study.
Programmed cell death and cancer
Authors: Sun Y , Peng Z-L 
Published: April 2009

Abstract
Programmed cell death (PCD) is an important terminal pathway for cells of multicellular organisms, and is involved in a variety of biological events that include morphogenesis, maintenance of tissue homeostasis, and elimination of harmful cells. Dysfunction of PCD leads to various diseases in humans, especially various cancers. Accumulating evidence indicates that PCD is closely related to anti-cancer therapy. Recently, many studies have subdivided PCD into the three categories: apoptosis, autophagy, and programmed necrosis, based on criteria such as morphological alterations, initiating death signal, and the activation of caspases. In this article, we will review the main features and functions of all three types of programmed cell death, focusing on their roles in tumour cells and the relationship of the three types of cell death in anti-cancer therapy.
Health professionals and human rights campaigners: different cultures, shared goals
Authors: Sheather J 
Published: April 2009

AbstractThis article looks at a disagreement that emerged at an international human rights conference between health professionals and human rights activists. The disagreement centred on the scope of the responsibilities of health professionals in relation to potential systemic human rights violations. In this article, the nature of the disagreement that emerged at the conference is explored. It is first situated in relation to a strong shared commitment to the “right of everyone to the highest attainable standard of physical and mental health”—often shortened to “the right to health” as it appears in the International Covenant on Economic, Social and Cultural Rights (ICESCR). Some of the tensions that emerged between the participants are then looked at and some of the causes of apparent disagreement identified. The relevance of human rights to health professionals and their impact on medical practice are discussed. Finally, it is argued that, given the common interests shared by these groups, the misunderstandings are not substantive and that there is real scope for mutual learning and collaboration. Although the conference was in southern Asia, the lessons learnt are applicable anywhere in the world—they are equally as relevant to the UK and Europe as to developing countries in the south.
Risk factors of biliary complications following liver transplantation: retrospective analysis of a single centre
Authors: Yuan D , Wei Y-G , Lin H-M , Li F-Q , Yang M , Liu X-L , Li B , Yan L-N , Zeng Y , Wen T-F , Zhao J-C , Yang J-Y 
Published: April 2009

Abstract

Background
Despite improvements that have been achieved in surgical techniques and organ preservation, biliary complications remain one of the most serious morbidities following liver transplantation. However, factors related to biliary complications after liver transplantation are not completely understood. The objective of this study was to identify retrospectively possible risk factors of biliary complications following liver transplantation.

Methods
Data on 279 patients who underwent liver transplantation between January 1999 and November 2005 were collected retrospectively. Selected variables from preoperative, intraoperative and postoperative data were first analysed using univariate logistic regression. Filtered factors with p&lt;0.1 in the first step were further investigated to identify factors independently associated with biliary complications following liver transplantation.

Results
The overall incidence of biliary complications was 22.6%. Multivariate regression revealed that biliary cirrhosis (p = 0.038), anhepatic phase time (p = 0.04), and incidence of hepatic artery abnormality (p = 0.001) after transplantation were factors that were significantly related to biliary complications. Use of a T tube for biliary reconstruction and living grafts were not associated with biliary complications following liver transplantation.

Conclusion
This study suggests that further technical refinement—namely, shortening the anhepatic phase duration, shielding the hepatic artery, and refining biliary duct reconstruction—can reduce the incidence of biliary complications following liver transplantation.
Ileal MALT lymphoma causing massive gastrointestinal haemorrhage revealed on computed tomography angiography
Authors: Marks D J B , Prodromou A , Silvanto A , Cox A , Pakzad F , Train M , Mitchell I C 
Published: April 2009

Abstract
Primary MALT lymphomas affecting the ileum are rare, and their presentation with massive haemorrhage exceptional. This report describes such a case. The patient presented with melaena and haemodynamic instability, but normal upper gastrointestinal endoscopy. Subsequent imaging with multi-detector row computed tomography angiography both localised the bleeding source to the ileum and identified the underlying tumour, resulting in considerably earlier introduction of appropriate management. The patient made an excellent recovery and remains in remission.
Impacts of episodic acidification on in-stream survival and physiological impairment of Atlantic salmon (Salmo salar) smolts
Authors: McCormick Stephen D. , Keyes Amanda , Nislow Keith H. , Monette Michelle Y. 
Published: April 2009

We conducted field studies to determine the levels of acid and aluminum (Al) that affect survival, smolt development, ion homeostasis, and stress in Atlantic salmon ( Salmo salar ) smolts in restoration streams of the Connecticut River in southern Vermont, USA. Fish were held in cages in five streams encompassing a wide range of acid and Al levels for two 6-day intervals during the peak of smolt development in late April and early May. Physiological parameters were unchanged from initial sampling at the hatchery and the high water quality reference site (pH > 7.0, inorganic Al < 12 μg·L–1). Mortality, substantial loss of plasma chloride, and gill Na+/K+-ATPase activity, and elevated gill Al occurred at sites with the lowest pH (5.4–5.6) and highest inorganic Al (50–80 μg·L–1). Moderate loss of plasma chloride, increased plasma cortisol and glucose, and moderately elevated gill Al occurred at less severely impacted sites. Gill Al was a better predictor of integrated physiological impacts than water chemistry alone. The results indicate that Al and low pH under field conditions in some New England streams can cause mortality and impair smolt development in juvenile Atlantic salmon and provide direct evidence that episodic acidification is impacting conservation and recovery of Atlantic salmon in the northeastern USA.
Behavioral responses of juvenile weakfish (Cynoscion regalis) to diel-cycling hypoxia: swimming speed, angular correlation, expected displacement, and effects of hypoxia acclimation
Authors: Brady Damian C. , Targett Timothy E. , Tuzzolino Danielle M. 
Published: April 2009

Areas of low flushing and high nutrient loading in shallow estuaries are susceptible to diel-cycling hypoxia and also represent important nursery habitat for juvenile estuary-dependent fishes. Swimming speed, angular correlation, and expected displacement were measured in juvenile weakfish ( Cynoscion regalis ) in response to diel-cycling hypoxia (cycling between 7.0 and 0.4 mg O2·L–1). Saturation-acclimated (7.0 mg O2·L–1) weakfish exhibited an active response by increasing swimming speed (to a maximum at 2.8 mg O2·L–1) and angular correlation (to a maximum at 1.4 mg O2·L–1) as dissolved oxygen (DO) decreased, after which weakfish exhibited a passive response and both swimming speed and angular correlation decreased by ~50% and 70%, respectively, at 0.4 mg O2·L–1. Weakfish acclimated to hypoxia (cycling between 2.0 and 11.0 mg O2·L–1for 10 days) did not vary swimming speed during decreasing DO or DO recovery (increasing DO) and had an overall swimming speed 46% lower than saturation-acclimated weakfish at 7.0 mg O2·L–1. At the end of DO recovery, saturation- and hypoxia-acclimated weakfish had recovered 60% and 80% of their initial swimming speeds, respectively. The relationship between previous hypoxia exposure and behavior may be an important determinant of habitat utilization in estuarine nursery areas impacted by diel-cycling hypoxia.