2,224 research outputs found
Differential inhibition of postnatal brain, spinal cord and body growth by a growth hormone antagonist
BACKGROUND: Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH. RESULTS: Before 50 days of postnatal age, GHA reduces spinal cord weight more than brain weight, but less than body weight. Thereafter, GHA ceases to inhibit the increase in body weight, which approaches control levels by day 150. In contrast, GHA continues to act on the CNS after day 50, reducing spinal cord growth to a greater extent and for a longer duration than brain growth. CONCLUSIONS: Judging from its inhibition by GHA, GH differentially affects the magnitude, velocity and duration of postnatal growth of the brain, spinal cord and body. GH promotes body enlargement more than CNS growth early in postnatal life. Later, its CNS effects are most obvious in the spinal cord, which continues to exhibit GH dependence well into adulthood. As normal CNS growth slows, so does its inhibition by GHA, suggesting that reduced trophic effects of GH contribute to the postnatal slowing of CNS growth. GHA is a highly useful tool for studying the role of endogenous GH on organ-specific growth during aging
Non-invasive single-cell biomechanical analysis using live-imaging datasets
The physiological state of a cell is governed by a multitude of
processes and can be described by a combination of mechanical,
spatial and temporal properties. Quantifying cell dynamics at multiple
scales is essential for comprehensive studies of cellular function, and
remains a challenge for traditional end-point assays. We introduce an
efficient, non-invasive computational tool that takes time-lapse
images as input to automatically detect, segment and analyze
unlabeled live cells; the program then outputs kinematic cellular
shape and migration parameters, while simultaneously measuring
cellular stiffness and viscosity. We demonstrate the capabilities of the
program by testing it on human mesenchymal stem cells (huMSCs)
induced to differentiate towards the osteoblastic (huOB) lineage, and
T-lymphocyte cells (T cells) of naïve and stimulated phenotypes. The
program detected relative cellular stiffness differences in huMSCs
and huOBs that were comparable to those obtained with studies that
utilize atomic force microscopy; it further distinguished naïve from
stimulated T cells, based on characteristics necessary to invoke an
immune response. In summary, we introduce an integrated tool to
decipher spatiotemporal and intracellular dynamics of cells, providing
a new and alternative approach for cell characterization
Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma
Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population
Silent cerebral infarct after cardiac catheterization as detected by diffusion weighted Magnetic Resonance Imaging: a randomized comparison of radial and femoral arterial approaches
Background and objective: Cerebral microembolism detected by transcranial Doppler (TCD) occurs systematically
during cardiac catheterization, but its clinical relevance, remains unknown. Studies suggest that asymptomatic embolic
cerebral infarction detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac interventions with
a frequency as high as 15 to 22% of cases. We have set up, for the first time, a prospective multicenter trial to assess the
rate of silent cerebral infarction after cardiac catheterization and to compare the impact of the arterial access site,
comparing radial and femoral access, on this phenomenon.
Study design: This prospective study will be performed in patients with severe aortic valve stenosis. To assess the
occurrence of cerebral infarction, all patients will undergo cerebral DW-MRI and neurological assessment within 24
hours before, and 48 hours after cardiac catheterization and retrograde catheterization of the aortic valve.
Randomization for the access site will be performed before coronary angiography. A subgroup will be monitored by
transcranial power M-mode Doppler during cardiac catheterization to observe cerebral blood flow and track emboli.
Neuropsychological tests will also be recorded in a subgroup of patients before and after the interventional procedures
to assess the impact of silent brain injury on potential cognitive decline. The primary end-point of the study is a direct
comparison of ischemic cerebral lesions as detected by serial cerebral DW-MRI between patients explored by radial
access and patients explored by femoral access. Secondary end-points include comparison of neuropsychological test
performance and number of microembolism signals observed in the two groups.
Implications: Using serial DW-MRI, silent cerebral infarction rate will be defined and the potential influence of vascular
access site will be evaluated. Silent cerebral infarction might be a major concern during cardiac catheterization and its
potential relationship to cognitive decline needs to be assessed.
Study registration: The SCIPION study is registered through National Institutes of Health-sponsored clinical trials
registry and has been assigned the Identifier: NCT 00329979
Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma
BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre
Antifungal activity of a novel chromene dimer
The activity on Aspergillus spp. growth and on ochratoxin A production of two novel chromene dimers (3) was evaluated. The results of the bioassays indicate that the chromene dimer 3a inhibited mycelia growth by approximately 50% (EC50) at 140.1 μmol L−1 for A. niger, 384.2 μmol L−1 for A. carbonarius, 69.1 μmol L−1 for A. alliaceus and 559.1 μmol L−1 for A. ochraceus. When applied at concentrations of 2 mmol L−1, 3a totally inhibited the growth of all Aspergillus spp. tested. Furthermore, ochratoxin A production by A. alliaceus was reduced by about 94% with a 200 μmol L−1 solution of this compound. A moderate inhibitory effect was observed for the analogous structure 3b on ochratoxin A production but not in mycelia growth. No inhibition was registered for compounds 2a and 2b, used as synthetic precursors of the dimeric species 3.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/
11228/2002
Coverage, Continuity and Visual Cortical Architecture
The primary visual cortex of many mammals contains a continuous
representation of visual space, with a roughly repetitive aperiodic map of
orientation preferences superimposed. It was recently found that orientation
preference maps (OPMs) obey statistical laws which are apparently invariant
among species widely separated in eutherian evolution. Here, we examine whether
one of the most prominent models for the optimization of cortical maps, the
elastic net (EN) model, can reproduce this common design. The EN model
generates representations which optimally trade of stimulus space coverage and
map continuity. While this model has been used in numerous studies, no
analytical results about the precise layout of the predicted OPMs have been
obtained so far. We present a mathematical approach to analytically calculate
the cortical representations predicted by the EN model for the joint mapping of
stimulus position and orientation. We find that in all previously studied
regimes, predicted OPM layouts are perfectly periodic. An unbiased search
through the EN parameter space identifies a novel regime of aperiodic OPMs with
pinwheel densities lower than found in experiments. In an extreme limit,
aperiodic OPMs quantitatively resembling experimental observations emerge.
Stabilization of these layouts results from strong nonlocal interactions rather
than from a coverage-continuity-compromise. Our results demonstrate that
optimization models for stimulus representations dominated by nonlocal
suppressive interactions are in principle capable of correctly predicting the
common OPM design. They question that visual cortical feature representations
can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure
HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4+ T Cell Responses
BACKGROUND: Identification of human leukocyte antigen class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes from influenza virus is of importance for the development of new effective peptide-based vaccines. METHODOLOGY/PRINCIPAL FINDINGS: In the present work, bioinformatics was used to predict 9mer peptides derived from available influenza A viral proteins with binding affinity for at least one of the 12 HLA-I supertypes. The predicted peptides were then selected in a way that ensured maximal coverage of the available influenza A strains. One hundred and thirty one peptides were synthesized and their binding affinities for the HLA-I supertypes were measured in a biochemical assay. Influenza-specific T cell responses towards the peptides were quantified using IFNgamma ELISPOT assays with peripheral blood mononuclear cells (PBMC) from adult healthy HLA-I typed donors as responder cells. Of the 131 peptides, 21 were found to induce T cell responses in 19 donors. In the ELISPOT assay, five peptides induced responses that could be totally blocked by the pan-specific anti-HLA-I antibody W6/32, whereas 15 peptides induced responses that could be completely blocked in the presence of the pan-specific anti-HLA class II (HLA-II) antibody IVA12. Blocking of HLA-II subtype reactivity revealed that 8 and 6 peptide responses were blocked by anti-HLA-DR and -DP antibodies, respectively. Peptide reactivity of PBMC depleted of CD4(+) or CD8(+) T cells prior to the ELISPOT culture revealed that effectors are either CD4(+) (the majority of reactivities) or CD8(+) T cells, never a mixture of these subsets. Three of the peptides, recognized by CD4(+) T cells showed binding to recombinant DRA1*0101/DRB1*0401 or DRA1*0101/DRB5*0101 molecules in a recently developed biochemical assay. CONCLUSIONS/SIGNIFICANCE: HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4(+) T cell responses restricted by HLA-II molecules
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