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Mycobacterium avium subspecies paratuberculosis (MAP) can cause a chronic inflammatory bowel disease, Johne's disease (JD), in ruminant animals. This study has explored the molecular basis of resistance and susceptibility to this disease in red deer breeds previously confirmed to express polarised phenotypes by experimental infection trials and following natural infection. Monocyte-derived macrophage cultures were obtained from uninfected red deer selected for either a resistant or susceptible phenotype. Cells were infected with MAP in vitro and gene expression analysed by RNA-Seq. Transcriptome analysis revealed a more disrupted gene expression profile in macrophages from susceptible animals compared with cells from resistant animals in terms of the number of genes up- or downregulated. Highly upregulated genes were related to chemotaxis (CXCL10, CSF3, and CCL8) and type 1 interferon signalling (RSAD2, IFIT1, IFIT2, ISG12, ISG15, USP18, and HERC6). Upregulation of these genes was observed to be greater in macrophages from susceptible animals compared to cells from resistant animals in response to in vitro MAP infection. These data support the use of transcriptomic approaches to enable the identification of markers associated particularly with susceptibility to MAP infection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Mycobacterium avium subsp. paratuberculosis [MAP], the causative agent of enteric Johne's disease, incurs significant economic losses to the livestock industry. Prophylactic vaccination can be employed as a control means, however mineral oil-based vaccines currently in practice have limited efficacy, produce strong antibody responses that confound serological diagnostic testing, and cause severe injection site reactions. In the present study, the safety and efficacy of a commercial mineral oil-adjuvanted vaccine (Gudair) was compared with novel parenteral-route vaccines in sheep; these comprised live or heat-killed (HK) whole cell preparations of MAP strain 316F, formulated into a food-grade lipid vaccine delivery matrix. Subcutaneous administration of lipid-formulated live or HK 316F-induced significantly fewer adverse injection site reactions than Gudair; adverse injection site reactions were eliminated altogether by intraperitoneal (i.p.) injection of lipid-formulated live 316F. Injections of lipid-formulated 316F-induced significant peripheral blood cell-mediated immune (CMI) responses in the absence of antibody, while Gudair-induced strong antibody and CMI reactivity. Vaccinated and non-vaccinated control sheep were challenged via oral inoculation of a virulent MAP isolate, and disease progress was monitored for 16 months, followed by necropsy. All vaccine regimes reduced the overall pathological grading of biopsied intestinal tract (IT) tissues; among these, only Gudair promoted a significant reduction in the incidence of histopathological IT lesions, while only i.p. injection of lipid-formulated live 316F significantly reduced the incidence of gross IT lesions. All lipid-formulated vaccines (but not Gudair) significantly reduced the incidence of bacteriological culture-confirmed MAP infection. This study identifies a new vaccination strategy against Johne's disease in sheep using conventional MAP vaccine strains formulated in a metabolisable lipid delivery matrix.

Tuberculosis due to Mycobacterium spp. continues to represent a major threat to human and animal health, prompting the search for effective vaccines. We have previously reported a sequential prime and boost homologous vaccination regime, using live avirulent M. bovis bacille Calmette-Guerin (BCG) strain 1173P2, that can provide significant protection to red deer (Cervus elaphus) against virulent M. bovis infection. Here, we have investigated the influence of varying the time-periods during and following the vaccination regime on the subsequent outcome of disease following post-vaccination pathogen challenge. Deer vaccinated using the standard regime of BCG-prime (week 0) and BCG-boost (week 8) followed by M. bovis challenge (week 14-16) were highly protected, showing significant reductions in the incidence of M. bovis infection and tuberculous lesions, as well as reduced pathogen burdens in sentinel lymphatic tissues. Decreasing the time-period between primary and secondary immunisations from 8 to 4 weeks had no significant impact on the protective efficacy afforded by BCG vaccination, while increasing this period to 43 weeks largely ablated protection. Increasing the time-period between secondary immunisation and M. bovis challenge from 6 to 26 or 52 weeks also had no significant impact on protection, suggesting that an appropriately timed BCG prime-boost vaccination regime can establish long-lasting protective immunological memory in deer. Finally, increasing the time-period between virulent M. bovis challenge and the subsequent post-mortem examination of disease outcome indicated that - once vaccinated by the standard prime-boost regime - deer remain refractory to disease if challenged and maintained for up to 52 weeks, suggesting that vaccinated animals harbouring low numbers of virulent M. bovis organisms do not succumb to disease activation over time. These findings are discussed in relation to concurrent measurements of in vivo and ex vivo immunological markers of disease and protection, as well as the wider implications of a standardised vaccine regimen for practical use in animal health.

Johne's disease in ruminants is caused by the pathogenic bacterium Mycobacterium avium subspecies paratuberculosis (Map). Currently available Map commercial vaccines protect against clinical disease but not infection. In this study, the proprietary Johne's vaccine Neoparasec and an aqueous formulation of Map 316F (AquaVax) were tested in sheep. Detailed immunological examination of blood and gut-associated lymphoid tissues was carried out on animals after vaccination and challenge with virulent Map to identify markers of protective immunity. Neoparasec vaccination provided significant protection against disease while AquaVax did not. Immune animals had stronger cell-mediated responses and altered proportions of CD4+, CD8+, CD25+ and B cells in blood, spleen and the gut lymphatics, than diseased animals.

Enzymes that modulate the level of circulating steroid hormone can be used to combat steroid-dependent disorders. Members of the NADPH-dependent short chain dehydrogenase/reductase (SDR) family control blood pressure, fertility, and natural and neoplastic growth. Despite the fact that only one amino acid residue is strictly conserved in the 60 known members of the family, all appear to have the dinucleotide-binding Rossmann fold and homologous catalytic residues containing the conserved tyrosine. Variation in the amino acid composition of the substrate binding pocket creates specificity of binding for steroids, prostaglandins, sugars and alcohols. Licorice induces high blood pressure by inhibiting an SDR in the kidney, and appears to combat ulcers by inhibiting another in the stomach. Detailed X-ray analyses of various members of the family should allow the design of potent, tissue-specific, highly selective inhibitors.

We used the Farnsworth-Munsell 100 Hue Test to study the incidence of acquired color vision defects in 16 patients with unilateral and and seven patients with bilateral retrobulbar optic neuritis whose visual acuity had recovered to 6/12 (20/40) or better. We recorded the visual-evoked response to a pattern stimulus on the same day. All 30 affected eyes showed an excessive number of errors on Farnsworth-Munsell 100 Hue testing. The number of errors increased with greater residual optic nerve damage. One false-positive and two false-negative visual-evoked responses were found.

In two women, 26 and 24 years old, respectively, polytomography revealed optic canal fractures. The investigation of visual loss after orbital or otolaryngologic surgery included tomography of the optic canals to rule out compression of the intracanalicular optic nerve.

A 59-year-old man with a previous left frontal lobe infarction sustained an infarction of the right frontal lobe. The patient manifested a bilateral symmetrical blepharoptosis that resolved in two months. Eyelid movements seem to be bilaterally represented in the frontal lobes. Bilateral cortical disease can produce supranuclear eyelid abnormalities such as blepharoptosis, difficulty maintaining eyelid position, and difficulty initiating eyelid movement.