Generation of human antibody fragments against Streptococcus mutans using a phage display chain shuffling approach

BACKGROUND: Common oral diseases and dental caries can be prevented effectively by passive immunization. In humans, passive immunotherapy may require the use of humanized or human antibodies to prevent adverse immune responses against murine epitopes. Therefore we generated human single chain and diabody antibody derivatives based on the binding characteristics of the murine monoclonal antibody Guy's 13. The murine form of this antibody has been used successfully to prevent Streptococcus mutans colonization and the development of dental caries in non-human primates, and to prevent bacterial colonization in human clinical trials. RESULTS: The antibody derivatives were generated using a chain-shuffling approach based on human antibody variable gene phage-display libraries. Like the parent antibody, these derivatives bound specifically to SAI/II, the surface adhesin of the oral pathogen S. mutans. CONCLUSIONS: Humanization of murine antibodies can be easily achieved using phage display libraries. The human antibody fragments bind the antigen as well as the causative agent of dental caries. In addition the human diabody derivative is capable of aggregating S. mutans in vitro, making it a useful candidate passive immunotherapeutic agent for oral diseases

Ligamentous rupture of the ACL associated with dislocated fracture of the proximal tibial physis in a 12-year-old boy

BACKGROUND: Dislocated fracture of the proximal physeal plate of the tibia with or without metaphyseal fragment is rare in children. This unusual fracture classically excludes rupture of the anterior cruciate ligament due to the ligament's stability. A combination of both injuries has not been previously published in the literature. CASE PRESENTATION: The authors report the case of a 12-year-old boy who presented with a dislocated fracture (Salter-Harris II) of the proximal tibia combined with ligamentous rupture of the anterior cruciate ligament after a sporting accident

Clinical course, costs and predictive factors for response to treatment in carpal tunnel syndrome: The PALMS study protocol

Background Carpal tunnel syndrome (CTS) is the most common neuropathy of the upper limb and a significant contributor to hand functional impairment and disability. Effective treatment options include conservative and surgical interventions, however it is not possible at present to predict the outcome of treatment. The primary aim of this study is to identify which baseline clinical factors predict a good outcome from conservative treatment (by injection) or surgery in patients diagnosed with carpal tunnel syndrome. Secondary aims are to describe the clinical course and progression of CTS, and to describe and predict the UK cost of CTS to the individual, National Health Service (NHS) and society over a two year period. Methods/Design In this prospective observational cohort study patients presenting with clinical signs and symptoms typical of CTS and in whom the diagnosis is confirmed by nerve conduction studies are invited to participate. Data on putative predictive factors are collected at baseline and follow-up through patient questionnaires and include standardised measures of symptom severity, hand function, psychological and physical health, comorbidity and quality of life. Resource use and cost over the 2 year period such as prescribed medications, NHS and private healthcare contacts are also collected through patient self-report at 6, 12, 18 and 24 months. The primary outcome used to classify treatment success or failures will be a 5-point global assessment of change. Secondary outcomes include changes in clinical symptoms, functioning, psychological health, quality of life and resource use. A multivariable model of factors which predict outcome and cost will be developed. Discussion This prospective cohort study will provide important data on the clinical course and UK costs of CTS over a two-year period and begin to identify predictive factors for treatment success from conservative and surgical interventions

Lower respiratory tract infection and rapid expansion of an abdominal aortic aneurysm: a case report

<p>Abstract</p> <p>Introduction</p> <p>The rate of abdominal aortic aneurysm expansion is related to multiple factors. There is some evidence that inflammation can accelerate aneurysm expansion. However, the association between pulmonary sepsis and rapid abdominal aortic aneurysm expansion is rarely reported.</p> <p>Case presentation</p> <p>Here we present a case of a rapidly expanding abdominal aortic aneurysm in a 68-year-old Caucasian man with a concomitant lower respiratory tract infection and systemic sepsis requiring intensive monitoring and urgent endovascular intervention. Our patient had an uncomplicated post-operative recovery and a follow-up computed tomography scan at one month demonstrated no evidence of an endoleak.</p> <p>Conclusion</p> <p>This case highlights the potential association between pulmonary sepsis and rapid abdominal aortic aneurysm expansion. In such cases, a policy of frequent monitoring should be adopted to identify those patients requiring definitive management.</p

Preparing the Perfect Cuttlefish Meal: Complex Prey Handling by Dolphins

Dolphins are well known for their complex social and foraging behaviours. Direct underwater observations of wild dolphin feeding behaviour however are rare. At mass spawning aggregations of giant cuttlefish (Sepia apama) in the Upper Spencer Gulf in South Australia, a wild female Indo-Pacific bottlenose dolphin (Tursiops aduncus) was observed and recorded repeatedly catching, killing and preparing cuttlefish for consumption using a specific and ordered sequence of behaviours. Cuttlefish were herded to a sand substrate, pinned to the seafloor, killed by downward thrust, raised mid-water and beaten by the dolphin with its snout until the ink was released and drained. The deceased cuttlefish was then returned to the seafloor, inverted and forced along the sand substrate in order to strip the thin dorsal layer of skin off the mantle, thus releasing the buoyant calcareous cuttlebone. This stepped behavioural sequence significantly improves prey quality through 1) removal of the ink (with constituent melanin and tyrosine), and 2) the calcareous cuttlebone. Observations of foraging dolphin pods from above-water at this site (including the surfacing of intact clean cuttlebones) suggest that some or all of this prey handling sequence may be used widely by dolphins in the region. Aspects of the unique mass spawning aggregations of giant cuttlefish in this region of South Australia may have contributed to the evolution of this behaviour through both high abundances of spawning and weakened post-spawning cuttlefish in a small area (>10,000 animals on several kilometres of narrow rocky reef), as well as potential long-term and regular visitation by dolphin pods to this site

The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Risk and prognostic significance of tuberculosis in patients from The TREAT Asia HIV Observational Database

10.1186/1471-2334-9-46BMC Infectious Diseases94

Quorum Sensing Influences Vibrio harveyi Growth Rates in a Manner Not Fully Accounted For by the Marker Effect of Bioluminescence

The light-emitting Vibrios provide excellent material for studying the interaction of cellular communication with growth rate because bioluminescence is a convenient marker for quorum sensing. However, the use of bioluminescence as a marker is complicated because bioluminescence itself may affect growth rate, e.g. by diverting energy. quorum mutants. growth rate can be either positive or negative and includes both bioluminescence-dependent and independent components. Bioluminescence tends to slow growth rate but not enough to account for the effects of quorum sensing on growth rate