Host defences against Aspergillus Fumigatus

The potential of the filamentous fungus Aspergillus fumigatus to act as an opportunistic pathogen may be related to its ability to resist the host defence network. Whilst phagocytic cells are clearly important in host defences against invading microorganisms their precise role in the killing of A. fumigatus remains undefined.The purpose of this study was to examine the basic interactions between phagocytic cells, from humans and rodents, with spores of A. fumigatus. In particular the mechanisms whereby phagocytic cells bind and kill spores of A. fumigatus, when compared with the relatively non-pathogenic fungus Penicillium ochrochloron were investigated.In order to investigate why people with asthma may develop some hypersensitivity reactions to A. fumigatus, in particular, rather than to the many other fungi in the atmosphere, the possibility that there may be a defect in the handling of the fungus by such patients has been tested. A comparison of the fungal handling by phagocytes from asthmatic patients, both sensitised and unsensitised to A. fumigatus with phagocytes from non-asthmatic subjects has been made.The principal findings from this study are that spores of A. fumigatus bind to the surface of the phagocytic cell yet are relatively resistant to phagocytosis. The spores also fail to trigger the phagocytic cells into releasing the potentially microbicidal reactive oxygen intermediates. These results may be related to a further finding which is that spores of A. fumigatus release a low molecular weight substance (diffusate) which interferes with various aspects of phagocytic cell activation. Spore diffusates were shown to inhibit the phagocytosis of radiolabelled antibody-coated sheep red blood cells and to suppress the spontaneous release of reactive oxygen intermediates by Corynebacterium parvum stimulated mouse peritoneal exudate cells. In addition spores diffusates inhibited the ability of phagocytic cells to spread on glass and reduce the number of phagocytic cells migrating towards a known chemoattractant.Studies on spore killing showed that spores of A. fumigatus opsonised in autologous serum were more resistant to killing by phagocytic cells from humans and rodents than similarly opsonised spores of P. ochrochloron. However, the ability of the phagocytic cells to kill spores of A. fumigatus was substantially increased when the spores were opsonised in sera which had been heat-treated for 30 minutes at 56°C. No increased killing was found with P. ochrochloron.People with asthma sensitised to A. fumigatus showed significant differences in their handling of A. fumigatus in vitro when compared with the control group. Monocytes from these sensitised patients killed significantly fewer spores of A. fumigatus (opsonised in auto¬ logous sera) whilst their polymorphonuclear leucocytes killed significantly more. No such differences were found for P. ochrochloron.The work reported in this Thesis has given us a clearer understanding of why Aspergillus fumigatus is an important cause of disease in man, and how the defence mechanisms that it has evolved in its natural environment the soil, enable it to act as a saprophyte or parasite in the lungs of humans and animals. The results also suggest a mechanism whereby heat-labile serum components may be an advantage to the survival of the fungus, thus perhaps explaining why it may be a particular problem in the airways of asthmatic patients

Host response to cuckoo song is predicted by the future risk of brood parasitism

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Risk assessment occurs over different temporal and spatial scales and is selected for when individuals show an adaptive response to a threat. Here, we test if birds respond to the threat of brood parasitism using the acoustical cues of brood parasites in the absence of visual stimuli. We broadcast the playback of song of three brood parasites (Chalcites cuckoo species) and a sympatric non-parasite (striated thornbill, Acanthiza lineata) in the territories of superb fairy-wrens (Malurus cyaneus) during the peak breeding period and opportunistic breeding period. The three cuckoo species differ in brood parasite prevalence and the probability of detection by the host, which we used to rank the risk of parasitism (high risk, moderate risk, low risk). Results: Host birds showed the strongest response to the threat of cuckoo parasitism in accordance with the risk of parasitism. Resident wrens had many alarm calls and close and rapid approach to the playback speaker that was broadcasting song of the high risk brood parasite (Horsfield’s bronze-cuckoo, C. basalis) across the year (peak and opportunistic breeding period), some response to the moderate risk brood parasite (shining bronze-cuckoo, C. lucidus) during the peak breeding period, and the weakest response to the low risk brood parasite (little bronzecuckoo, C. minutillus). Playback of the familiar control stimulus in wren territories evoked the least response. Conclusion: Host response to the threat of cuckoo parasitism was assessed using vocal cues of the cuckoo and was predicted by the risk of future parasitism

Phosphoinositide metabolism and prostacyclin formation in retinal microvascular endothelium: Stimulation by adenine nucleotides

Phosphoinositide lipid metabolism and prostacyclin production are implicated in endothelium dependent vascular relaxation in large blood vessels. To determine if these biochemical pathways might be involved in the regulation of microvascular tone in the retina, we measured the formation of 6-keto-prostaglandin-F1[alpha], the stable end product of prostacyclin, and inositol phosphates from 3H-labeled phosphoinositide lipids, in endothelial cells prepared from bovine retinal microvessels and maintained in long-term culture. We found that adenosine 5'-triphosphate and adenosine 5'-diphosphate both stimulated a dose-dependent accumulation of inositol phosphates and of 6-keto-prostaglandin-F1[alpha] in these cells. The agonist specificity of the responses, with stimulation by adenosine 5'-triphosphate and adenosine 5'-diphosphate, and inactivity of adenosine 5'-monophosphate and adenosine, suggest that they are mediated through P2 purinergic receptors. The similar early time courses of 6-keto-prostaglandin-F1[alpha] and inositol triphosphate production support the hypothesis that prostacyclin formation could result from the mobilization of intracellular calcium by inositol triphosphate, which activates phospholipase A, and thereby releases arachidonic acid to form prostacyclin. These findings point to a role for these cells in the regulation of normal retinal vascular tone. Because phosphoinositide lipid metabolism is altered in diabetes, dysfunction of these biochemical pathways in retinal endothelium could underlie the pathophysiology of diabetic retinopathy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28775/1/0000607.pd

Diagnosis of non-effusive feline infectious peritonitis by reverse transcriptase quantitative PCR from mesenteric lymph node fine-needle aspirates

The aim of this study was to evaluate a feline coronavirus (FCoV) reverse transcriptase quantitative PCR (RT-qPCR) on fine-needle aspirates (FNAs) from mesenteric lymph nodes (MLNs) collected in sterile saline for the purpose of diagnosing non-effusive feline infectious peritonitis (FIP) in cats. First, the ability of the assay to detect viral RNA in MLN FNA preparations compared with MLN biopsy preparations was assessed in matched samples from eight cats. Second, a panel of MLN FNA samples was collected from a series of cats representing non-effusive FIP cases (n = 20), FCoV-seropositive individuals (n = 8) and FCoV seronegative individuals (n = 18). Disease status of the animals was determined using a combination of gross pathology, histopathology and/or 'FIP profile', consisting of serology, clinical pathology and clinical signs. Viral RNA was detected in 18/20 non-effusive FIP cases; it was not detected in two cases that presented with neurological FIP. Samples from 18 seronegative non-FIP control cats and 7/8 samples from seropositive non-FIP control cats contained no detectable viral RNA. Thus, as a method for diagnosing non-effusive FIP, MLN FNA RT-qPCR had an overall sensitivity of 90.0% and specificity of 96.1%. In cases with a high index of suspicion of disease, RT-qPCR targeting FCoV in MLN FNA can provide important information to support the ante-mortem diagnosis of non-effusive FIP. Importantly, viral RNA can be reliably detected in MLN FNA samples in saline submitted via the national mail service. When applied in combination with biochemistry, haematology and serological tests in cases with a high index of suspicion of disease the results of this assay may be used to support a diagnosis of non-effusive FIP

Access to patients' clinical healthcare records: inclusion for community pharmacists in NHS Tayside.

The 2020 Workforce Vision in Scotland envisages 'making more and better use of technology ....to increase access to services and improve efficiency' across the healthcare interface. Services offered by community pharmacy remain limited by lack of shared access to patients' clinical information. In Scotland, every patient has a unique identifier, their CHI (community health index), which facilitates identification of/searching for patient records. The aim of this research was to explore the experiences of community pharmacists granted clinical portal access to patients' records

Effect of vaccination on transmission of SARS-CoV-2

No abstract available

Vaccination with Ad5 Vectors Expands Ad5-Specific CD8+ T Cells without Altering Memory Phenotype or Functionality

Adenoviral (Ad) vaccine vectors represent both a vehicle to present a novel antigen to the immune system as well as restimulation of immune responses against the Ad vector itself. To what degree Ad-specific CD8(+) T cells are restimulated by Ad vector vaccination is unclear, although such knowledge would be important as vector-specific CD8(+) T cell expansion could potentially further limit Ad vaccine efficacy beyond Ad-specific neutralizing antibody alone.Here we addressed this issue by measuring human Adenovirus serotype 5 (Ad5)-specific CD8(+) T cells in recipients of the Merck Ad5 HIV-1 vaccine vector before, during, and after vaccination by multicolor flow cytometry. Ad5-specific CD8(+) T-cells were detectable in 95% of subjects prior to vaccination, and displayed primarily an effector-type functional profile and phenotype. Peripheral blood Ad5-specific CD8(+) T-cell numbers expanded after Ad5-HIV vaccination in all subjects, but differential expansion kinetics were noted in some baseline Ad5-neutralizing antibody (Ad5 nAb) seronegative subjects compared to baseline Ad5 nAb seropositive subjects. However, in neither group did vaccination alter polyfunctionality, mucosal targeting marker expression, or memory phenotype of Ad5-specific CD8(+) T-cells.These data indicate that repeat Ad5-vector administration in humans expands Ad5-specific CD8(+) T-cells without overtly affecting their functional capacity or phenotypic properties. This is a secondary analysis of samples collected during the 016 trial. Results of the Merck 016 trial safety and immunogenicity have been previously published in the journal of clinical infectious diseases [1].ClinicalTrials.gov NCT00849680[http://www.clinicaltrials.gov/show/NCT00849680]