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Medical research on armour
Auton Neurosci. 2008 Jun 14;
Hoover DB, Shepherd AV, Southerland EM, Armour JA, Ardell JL
While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T(3) DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T(3) DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30-40% of ventricular afferent somata in T(3) DRG). About 30% of the ventricular afferent neurons in T(2) DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB(4). Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters.
Lancet. 2008 May 17; 371(9625): 1685-94
Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, Nicholson AG, O'Brien M, Peake M, Rudd R, Snee M, Steele J, Girling DJ, Nankivell M, Pugh C, Parmar MK,
BACKGROUND: Malignant pleural mesothelioma is almost always fatal, and few treatment options are available. Although active symptom control (ASC) has been recommended for the management of this disease, no consensus exists for the role of chemotherapy. We investigated whether the addition of chemotherapy to ASC improved survival and quality of life. METHODS: 409 patients with malignant pleural mesothelioma, from 76 centres in the UK and two in Australia, were randomly assigned to ASC alone (treatment could include steroids, analgesic drugs, bronchodilators, palliative radiotherapy [n=136]); to ASC plus MVP (four cycles of mitomycin 6 mg/m2, vinblastine 6 mg/m2, and cisplatin 50 mg/m2 every 3 weeks [n=137]); or to ASC plus vinorelbine (one injection of vinorelbine 30 mg/m2 every week for 12 weeks [n=136]). Randomisation was done by minimisation, with stratification for WHO performance status, histology, and centre. Follow-up was every 3 weeks to 21 weeks after randomisation, and every 8 weeks thereafter. Because of slow accrual, the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival. Analysis was by intention to treat. This study is registered, number ISRCTN54469112. FINDINGS: At the time of analysis, 393 (96%) patients had died (ASC 132 [97%], ASC plus MVP 132 [96%], ASC plus vinorelbine 129 [95%]). Compared with ASC alone, we noted a small, non-significant survival benefit for ASC plus chemotherapy (hazard ratio [HR] 0.89 [95% CI 0.72-1.10]; p=0.29). Median survival was 7.6 months in the ASC alone group and 8.5 months in the ASC plus chemotherapy group. Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone (HR 0.80 [0.63-1.02]; p=0.08), with a median survival of 9.5 months. There was no evidence of a survival benefit with ASC plus MVP (HR 0.99 [0.78-1.27]; p=0.95). We observed no between-group differences in four predefined quality-of-life subscales (physical functioning, pain, dyspnoea, and global health status) at any of the assessments in the first 6 months. INTERPRETATION: The addition of chemotherapy to ASC offers no significant benefits in terms of overall survival or quality of life. However, exploratory analyses suggested that vinorelbine merits further investigation.
Aging the oldest turtles: the placodont affinities of Priscochelys hegnabrunnensis.
Naturwissenschaften. 2008 May 9;
Scheyer TM
Priscochelys hegnabrunnensis, a fragmentary piece of armour shell from the Muschelkalk of Germany (Upper Triassic) with few diagnostic morphological features, was recently proposed to represent the oldest known stem turtle. As such, the specimen is of high importance because it shifts the date of the first appearance of turtles back about 20 Ma, which equals about 10% of the total stratigraphic range of the group. In this paper, I present new morphologic, histologic and neutron tomographic (NT) data that relate to the microstructure of the bone of the specimen itself. In opposition to the previous morphologic descriptions, P. hegnabrunnensis was found to share several distinctive features (i.e. bone sutures congruent with scute sulci, absence of a diploe structure with interior cancellous bone, thin vascular canals radiating outwards from distinct centres in each field and rugose ventral bone surface texture consisting of mineralised fibre bundles) with cyamodontoid placodonts (Diapsida: Sauropterygia) and fewer with stem turtles (i.e. depth of sulci). Two aspects that were previously thought to be relevant for the assignment to the turtle stem (conical scutes and presence of foramina) are argued to be of dubious value. P. hegnabrunnensis is proposed to represent a fragmentary piece of cyamodontoid armour consisting of fused conical plates herein. The specimen is not a part of the turtle stem and thus does not represent the oldest turtle. Accordingly, P. hegnabrunnensis does not shorten the ghost lineage to the potential sister group of turtles.
J Eukaryot Microbiol. 2008 May-Jun; 55(3): 185-200
Foissner W, Kusuoka Y, Shimano S
Levicoleps biwae n. gen., n. sp. was discovered in organic mud on the shore of Lake Biwa, Japan. Its morphology and small subunit rRNA gene sequence were studied with standard methods. Further, we established a terminology for the colepid armour and selected four features for genus recognition: the number of armour tiers, the structure of the tier plates, the presence/absence of armour spines, and the number of adoral organelles (three or five). The Japanese colepid, a barrel-shaped ciliate with an average size of 75 x 45 mum, has six armour tiers and hirtus-type tier plates, but lacks armour spines, both in the environment and in laboratory culture. Thus, it is considered to represent a new genus. This rank is supported by the considerable genetic distance (7%) from the common Coleps hirtus. Although L. biwae looks quite similar to C. hirtus in vivo, it is very likely most closely related to Coleps amphacanthus, a species with conspicuous armour spines, as indicated by body size, the number of ciliary rows and, especially, the multiple caudal cilia. Lake Biwa is about four million years old and inhabited by many endemic organisms, ranging from algae to large fish. Thus, we suspect that L. biwae is restricted to Lake Biwa or, at least, to Asia. Based on literature data and the generic features established, we also propose the new genus Reticoleps for Coleps remanei Kahl, 1933, and resurrect the genus Pinacocoleps Diesing, 1865 to include Coleps incurvus Ehrenberg, 1833, Coleps pulcher Spiegel, 1926, Coleps tessalatus Kahl, 1930 and, probably, Baikalocoleps quadratus Obolkina, 1995a. Nine colepid genera are diagnosed and dichotomously keyed.
Senior administrators of blood system acquitted of criminal charges in tainted blood tragedy.
HIV AIDS Policy Law Rev. 2007 Dec; 12(2-3): 42-3
On 1 October 2007, the Ontario Superior Court of Justice acquitted senior administrators of the blood system on charges of criminal negligence causing bodily harm and common nuisance related to the infection of haemophiliacs with HIV in 1986 and 1987. The victims, whose names were withheld due to a publication ban, had all used HT Factorate, a blood coagulation product used to treat haemophilia and manufactured by Armour, a pharmaceutical company based in New Jersey.
Fluorescein diacetate for determination of cell viability in tissue-engineered skin.
Tissue Eng Part C Methods. 2008 Mar; 14(1): 89-96
Armour AD, Powell HM, Boyce ST
Assurance of the quality of cultured skin substitutes (CSSs) currently relies on representative histology and determination of surface hydration, which provide limited sampling at selected points. To evaluate uniformity of cell density on the collagen matrices before clinical use, a field assessment of cell viability is advantageous. This study aimed to develop a field measure of cell viability in CSSs in vitro using fluorescein diacetate (FdA). CSSs were stained 3 days after keratinocyte inoculation using 0.04 mg/mL FdA followed by exposure to 366 nm of ultraviolet light. CSS fluorescence quantified using Metamorph image analysis was correlated with inoculation density, 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) values and histology of corresponding biopsies. CSS fluorescence correlated significantly with inoculation density (p < 0.001) and MTT values (p < 0.001) of biopsies collected immediately after FdA staining. Fluorescence at day 3 also predicted day 10 MTT values. No toxicity was detected in CSSs, and normal in vitro and in vivo histology was demonstrated after FdA exposure. In conclusion, measurement of intracellular fluorescence with FdA allows for the early, comprehensive measurement of cellular distributions and viability in engineered skin and may therefore facilitate quality assurance.
[Late respiratory function complications following burns.]
Rev Mal Respir. 2008 Mar; 25(3): 328-32
Ernesto S, Marduel Y, Freymond N, Pacheco Y, Devouassoux G
Introduction Twenty five per cent of thermal injuries are associated with secondary respiratory events linked to several mechanisms. In the acute phase of the accident oedema of the airways, the fume inhalation syndrome and ARDS are the most common causes responsible for death in 60% of cases. Late respiratory complications are little known and neglected. They comprise obstructive ventilatory defects due to the inhalation syndrome and restrictive defects secondary to ARDS or to dermal injury. Case report We report the case of a female patient, extensively burnt 2 years previously, admitted to hospital with severe acute respiratory failure complicating COPD. The presence of both restrictive and obstructive defects led to the suggestion of alternative underlying mechanisms such as the pulmonary consequences of ARDS and extensive dermal scars. The latter were responsible for an armour like thickening of the skin of the thorax compatible with the restrictive defect. Conclusions These functional abnormalities and the potential severity of acute respiratory failure are indications for regular pulmonary follow-up of patients with severe circumferential scarring of the thorax who are at high risk for respiratory complications.
Relationship between disc injury and manual lifting: a poroelastic finite element model study.
Proc Inst Mech Eng [H]. 2008 Feb; 222(2): 195-207
Natarajan RN, Williams JR, Lavender SA, An HS, Anderson GB
Understanding how failure originates in a lumbar motion segment subjected to loading conditions that are representative of manual lifting is important because it will pave the way for a better formulation of the exposure-injury relationship. The aim of the current investigation was to use a poroelastic finite element model of a human lumbar disc to determine its biomechanical characteristics under loading conditions that corresponded to three different, commonly occurring lifting activities and to identify the most hazardous type of loading with regard to damage to the disc. The current study showed that asymmetric lifting may increase the risk of back injury and pain. Lifting that involved lateral bending (asymmetric lifting) of the trunk was found to produce stresses at a localized area in the annulus, annuluar fibres, end plates, and facet joints that were higher than their respective tissue failure strength. Thus asymmetric lifting, if performed over a large number of cycles, might help to propagate this localized failure of the disc tissue to a larger area, owing to fatigue. The analyses also showed that largest fluid exchange between the nucleus and the end plates occurred during asymmetric lifting. If the fluid exchange is restricted owing to end plate calcification or sclerosis of the subchondral bone, high intradiscal pressure might develop, leading to higher disc bulge causing back pain.
Directional and balancing selection in human beta-defensins.
BMC Evol Biol. 2008; 8: 113
Hollox EJ, Armour JA
BACKGROUND: In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. RESULTS: We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93), is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. CONCLUSION: Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.
Theor Appl Genet. 2008 Apr 8;
Armour DJ, Mackie JM, Musial JM, Irwin JA
Five asymmetric hybrid plants were obtained between Medicago sativa (2n = 4x = 32) and Medicago arborea (2n = 4x = 32) through sexual reproduction and the use of a cytoplasmically male sterile M. sativa genotype. Over 2,000 pollinations were made to obtain these hybrids. Amplified fragment length polymorphism (AFLP) analysis showed that in the most studied hybrid (WA2273), 4% of the bands unique to the M. arborea parent were present, versus 72% for the unique M. sativa bands. This suggests that only a single M. arborea chromosome or chromosome parts has been transferred. WA2273 had 7% of AFLP bands which were not present in either parent, which is suggestive of chromosome rearrangements as would be expected if only chromosome parts or a single part had been transferred from M. arborea. Phenotypic evidence for hybridity was obtained for pod coiling (1.4 coils in WA2273 versus three coils in the M. sativa parent and its self and testcross populations, and one coil in M. arborea), and Colletotrichum trifolii race 2 resistance (transferred from the resistant M. arborea parent, as the M. sativa parent and the self populations were highly susceptible). The hybrids were self sterile, but were female fertile to a high level when crossed with 4x, but not 2x, M. sativa, indicating they were at or near 4x. Both the pod coiling trait and anthracnose resistance segregated in the progeny of testcrosses between WA2273 and M. sativa. The work demonstrates that agronomically useful traits can be introgressed into M. sativa from M. arborea by use of male sterile M. sativa and sexual reproduction.