The antigenicity of Mycoplasma mycoides, with particular reference to the polysaccharide antigens

Serum, plasma, lysed blood cells, urine and pleural fluid or lymph (inflammatory exudate from subcutaneous inoculation) were obtained from cattle naturally and artificially infected with Mycoplasma mycoides. These fluids were examined for antigens of M. mycoldes by means of the agar gel double diffusion precipitin test and the quantitative agar gel precipitin test. They were also examined for antibodies against M. mvcoides by means of the complement fixation and slide agglutination tests, and for viable M. tavcoides by growth in broth cultures. Hyperiimuune sera for use in these tests were prepared in sheep and cattle by the Intravenous injection of washed organisms that had been grown in broth medium. From the natural cases of CBPP viable organisms were obtained from the pleural fluid only, while in the experimental cases the organisms were present in the serum, plasma and lymph. Antibodies against M. mycoldes were demonstrated in sera and plasma samples of all cases. Specific precipitating antigens were demonstrated in all the fluids, urine possessing at least 5 serologically distinct antigens, lymph and pleural fluid at least 6 and serum and plasma at least 6 and sometimes 7 antigens. The 5 in urine were common to all fluids, while the extra 1 in lymph and pleural fluid was also present in serum and plasma. In addition to these so-called major antigens, minor ones, at least 6 in number, were also demonstrated, but these were apparently primarily associated with the organisms. The major precipitating antigens were predominantly extracellular with only small amounts present in the organisms. These major antigens were also elaborated by the organisms when grown In artificial culture medium, and those produced by fully virulent organisms were apparently identical to those produced by avirulent organisms.Fractionation of pooled urine from the artificially infected cattle by precipitation with varying volumes of cold iso-propyl alcohol and deproteinizatlon with a chlorofona-butanol mixture was undertaken. A total of 6 serologically distinct precipitating antigens were demonstrated in the AGT and separation of these antigens was possible to a limited extent by varying the volumes of alcohol used.Fraction C/l/2/3, the fraction which contained all the antigens, was shown to contain approximately 5.6 per cent. Kjeldahl N, 0.5 per cent. P., 42.4 per cent, carbohydrate (estimated as galactose) and 11.9 per cent, hexosamine. One or possibly 2 of the precipitin bands was shown to contain lipid, but there was no indication of nucleic acid. By the use of paper chromatography, galactose was demonstrated and probably sorbose and arahinose, together with some amino acids. These antigens were resistant to a temperature of 94°C. for 60 minutes and to the action of trypsin. Separation of the individual antigens was not obtained by either ultracentrifugation or electrophoresis. The antigenic fraction fixed complement in the presence of hyperimmune sheep sera, and fraction C/l/2/3 absorbed 87.5 and 96.9 per cent, of the agglutinating antibodies and 93.75 and 87.5 per cent, of the complement fixing antibodies from hyperimmune sheep x and sheep 6 sera respectively. This fraction was pyrogenic in rabbits and relatively non toxic to cattle, rabbits and mice, but proved to be lethal to fowl embryos. The antigens were haptens in cattle, rabbits and mice, but precipitating antibodies were produced in rabbits when the antigens were combined with "shiga conjugated protein". Fraction C/l/2/3 possessed an aggressive action when inoculated together with viable M. mycoides in immune animals and appeared to enhance the virulence of the organisms in susceptible cattle.It is suggested that these antigens play a part in assisting the growth of jf. mycoldes in the host tissues but are not in themselves significantly harmful

The Problem of Chilblains With a Note on Nicotinic Acid and Its Use in Their Treatment

The problem of chilblains is discussed as regards their aetiology and pathogenesis, It is claimed that nicotinic acid, given orally, has a specific effect on chilblains. Twenty seven cares are quoted to prove this, and it is strongly recommended as the treatment of choice in general practice owing to its ease of administration and its freedom from serious untoward effects. A brief note on nicotinic acid and its probable pharmacodynamics is appended

Studies on some bovine mycoplasmas

My studies on bovine mycoplasnas fall under three separate headings:A. ANGPLASMA MYQPI.DES VAR. MCOIDES AND CONTÁ2IOUS BOVINE UROPNEUMONIA. An investigation was undertaken to determine whether the allergic reaction could be developed as a useful diagnostic test for contagious bovine pleuropneumonia. Using antigens obtained from M. mycoides var. n coides two types of reaction were observed, an immediate reaction associated with lipopolysaccharide material and a delayed reaction associated with protein. It was impossible to separate the protein completely from the lipopolysaccharide, which elicited some non-specific reactions, and the test was abandoned.A comparison of various serological tests employed in contagious bovine pleuropneumonia diagnosis revealed that no single test was entirely satisfactory, but the complement fixation test was the best available. Growth inhibition of M. mycoides var. mycoides by serum was examined as a diagnostic test and as a measure of immunity. Two tests were evolved, one on solid medium and the other in liquid medium, and both proved to be of potential value for contagious bovine pleuropneumonia diagnosis, but their value in measuring immunity was not determined. Inhibition was observed, to occur in the absence of agglutination and heat-labile accessory factors.The lipopolysaccharide from M. mycoides var. mycoides, responsible for the immediate allergic reaction, was shown to be serologically related to a galactan extracted from normal bovine lung. This lipopolysaccharide was also shown to be aritigenically related to polysaccharides from a number of different sources including other microorganisms and this relationship was considered to be responsible for non-specific reactions discerned in diagnostic tests.It was suggested that the serological relationship between the lipopolysaccharide of M. Ayssides vay_t_mycoides and the galactan from bovine lung might play a role in the pathogenesis of contagious bovine pleuropneumonia. A preliminary examination of this percept was inconclusive, but it was shown, fortuitously, that immunity could be transferred passively.Electronmicroscopic examination of ItmmixleamaEl. ycoides, treated with specific antiserum, revealed a capsule or slime layer round the organisms. This capsule is probably composed of galactan.A method devised for the production, testing and transport of a modified Ti contagious bovine pleuropneumonia vaccine is described.Chicken embryos, from hens previously inoculated with M. mycoides var. mycoides, were immune to challenge with this organism, suggesting that the chicken embryo might be a suitable host for studying immunity to contagious bovine pleuropneumonia.B. MYCOPLASMAS WITH CALF NEUMONIA AND BOVINE KERATOCON'UNCTIVITIS. Material from pneumonic lungs cultured in special media resulted in the isolation of two species of xaycoplasma hitherto unrecorded from lungs. One was a new species of mycoplasma, subsequently named M. dispar, and the other was T-mycoplasna. Mycoplasmas were isolated from 75% of 65 pneumonic lungs examined; these comprised T-mycoplasmas from 58.5% of lungs, M. dispar from 51% and M. bovirhinis from 23%.The pathogenicity of the T-mycoplasmas was tested by inoculating cultures endobronchially into 3-week-old calves. Gross pneumonic lesions were observed in 14 out of the 16 calves at slaughter, compared with 2 out of 9 that revealed lesions following inoculation of control materials (P<0.01). Certain T-mycoplasmas also produced mastitis in the mammary glands of cows when inoculated via the teat canal. Strains both virulent and avirulent for the bovine mammary gland could be isolated from cattle, but human, canine and simian strains of T-mycoplasmas were avirulent. Bovine T-mycoplasmas were shown to be serologically heterogeneous.T-mycoplasmas, M. bovirhinis, Acholejlasma laidlawii and an unidentifiable species of mycoplasma were isolated from eyes of cattle suffering from keratoconjunctivitis.C. MYCOPLASMATALES VIRUSES Three distinct viruses have been isolated. All infect A. laidlawii producing visible plaques on 'lawns' of this organism. The first virus isolated, named Mycoplasmatales virus - laidlawii 1 (MV-L1), is a small (16 x 90 nm.) rod-shaped DNA containing virus. The second virus, named MV-L2, is roughly spherical, apparently enveloped and about 80 nm, in diameter (range 50-125 nm.). It appears to contain DNA and is serologically distinct from MV-Ll. The third virus (MV-L3), only recently isolated, is polyhedral and uniform in size (about 54 nm, diameter) and is serologically distinct from both MV-Li and MV-L2.PUBLICATIONS IN SUPPORT OF CANDIDATURE: A MYCOPLASMA MYCOIDES VAR. MYCOIDES AND CONTAGIOUS BOVINE PLEUROPNEUMONIA 1. GOURLAY, R. N. (1964). The allergic reaction in contagious bovine pleuropneumonia. Journal of Esylpáratiae2211-22122x 74, 286-299. || 2. & PALMER, R. F. (1965). Further studies on the allergic reaction in contagious bovine pleuropneumonia. Journal of Comparative Pathology 75, 89-95. || 3. & SHIFRINE, M. (1965) . Comparison between methods of antigen preparation and the use of adjuvant in the delayed allergic skin reaction in contagious bovine pleuropneumonia. Journal of Comparative Pathology 75, 375-380. || 4. SHIFRINE, M. & GOURLAY,. R. N. (1965). The immediate type allergic skin reaction in contagious bovine pleuropneumonia. Journal of Comparative Pathology 75, 381-385. || 5. & (1967). Serological relationships between Mycoplasma mycoides and other bacteria. Annals of the New York Academy of Science. 143, 311-324. || 6. GOURLAY, R. N. (1935). Comparison between some diagnostic tests for contagious bovine pleuropneumonia. Journal of Comparative Pathology 75, 97-109. || 7. SHIFRINE M. & GOURLAY, R. N. (1967). Evaluation of diagnostic tests for contagious bovine pleuropneumonia. ER112Iinafpizootic Diseases of Africa 15, 7-10, || 8. DOMERMUTH, C. H. & GOURLAY, R. N. (1967). A solid medium test for measuring growth inhibition and neutralisation of ypyARxçc2LdMcolasxes by immune bovine serum. Journal of General Microbiology 47, 289-294. || 9. GOURLAY, R. N. & DOMERMUTH, C. H. (1967). Growth inhibition and 'neutralisation' of Mycoplasma mycoides by immune bovine serum. Annals of the New York Academ of Science 143, 325-336. || 10. SHIFRINE, M. & GOURLAY, R. N. (1965). Serological relationship between galactans from normal bovine lung and Mycoplasma Nature, London 208, 498-499. || 11. GOURLAY, R. N. & SHIFRINE, M. (1966). Antigenic cross-reactions between the galactan from plasmanasoides and polysaccharides from other sources. Journal of Corn arative Patholoc 76, 417-425. || 12. & BROCKLESBY, D. W. (1967). Preliminary experiments with antigens of Theileria páLya (Theiler, 1904). British Veterinary_lamIlL 123, 533-540. || 13. & SHIFRINE, M. (1966). Passive transfer of immunity and formation of lung lesions following intravenous inoculation of Mycoplasma nix,21.sisa and immune bovine serum. Bulletin of Epiaslotic Diseases of Africa 14, 369-372. || 14. GOURLAY, R. N. & THROWER, K. J. (1968). Morl,hology of Llysgpjau_uarzlxcoides thread-phase growth. Journal of General Microbiology 54, 155-159. || 15. BROWN, R. D., GOURLAY, R. N. & MACLEOD, A. K. (1965). The production of Ti broth culture contagious bovine pleuropneumonia vaccine. Bulletin of E izootic Diseases of Africa 13, 149-155. || 16. GOURLAY, R. N. & MACLEOD, A. K. (1966). Fermentation of glucose by Mys2212sma mycoides and its effect on viability. Bulletin of E izootic Diseases of Africa 14, 373-381. || 17. & SHIFRINE, M. (1966). The use of embryonated chicken eggs for the study of immunity to MYcoplasma Tycoides. Veterinary Record 78, 256-257. || 18. & (1968). The virulence and viability of Mycoplasma mycoides strains in chicken embryos from normal and immunised hens. Research in Veterinary Science 9, 185-186. || B MYCOPLASMAS ASSOCIATED WITH CALF PNEUMONIA AND BOVINE KERATOCONJUNCTIVITIS: 19. GOURLAY, R. N. (1969). Isolation of a mycoplasma-like organism from pneumonic calf lungs. Veterinary Record 84, 229-230. || 20. & LEACH, R. H. (1970). A new mycoplasma species isolated from pneumonic lungs of calves (Mycoplasma dispar, Sp. Nov.) Journal of Medical Microbioloq 3, 111-123. || 21. (1968). The isolation of T-strains of Mycoplasma from pneumonic calf lungs. Research in Veterinar Science 9, 376-378. || 22. & THOMAS, L. H. (1969). The isolation of large colony and T-strain mycoplasmas from cases of bovine kerato-conjunctivitis. Veterinary Record 84, 416-417. || 23. & MACKENZIE, A. & COOPER, J. E. (1970). Studies of the microbiology and pathology of pneumonic lungs of calves. Journal of comparatitive Pathology 80, 575-584. || 24. & THOMAS, L. H. (1970). The experimental production of pneumonia in calves by the endobronchial inoculation of T-mycoplasmas. Journal of Com arative Patholoca 80, 585-594. || 25. HOWARD, C. J. & BROWNLIE, J. (1972). The production of mastitis in cows by the intramammary inoculation of T-mycoplasmas. Journal of Hygiene, Cambridge 70, 511-521. || 26. HOWARD, C. J. & GOURLAY, R. N. (1972). Serology of bovine T-mycoplasmas. British Veterinary Journal 128, XXXVII-XL. || 27. ______, _______ & BROWNLIE, J. (1973). The virulence of T-mycoplasmas, isolated from various animal species, assayed by intramammary inoculation in cattle. journal of Hygiene, Cambridge 71, 163-170. || C MYCOPLASMATALES VIRUSES: 28. GOURLAY, R. N. (1970). Isolation of a virus infecting a strain of MycopIasma laidlawii. Nature, London 225, 1165. || 29. , BRUCE, JUDY & GARWES , D. J. (1971). Characterisation of Mycoplasmatales virus laidlawii 1. Nature New Biolaay 229, 118-119. || 30. (1972). Ultrastructural studies of Mycoplasmatales viruses. MedicALILlIg. and Immunology 157, 172, || 31. BRUCE, J., GOURLAY R. N., HULL, R. & GARWES, D. J. (1972). Ultrastructure of Mycoplasmatales virus - laidlawii 1. Journal of 16, 215-221. || 32. GOURLAY, R. N. & WYLD, SARA G. (1972). Some biological characteristics of Mycoplasmatales virus laidlawii 1. Journal of General Virolgaz 14, 15-23. || 33. (1971). Mycoplasmatales virus - laidlawii 2, a new virus isolated from Acholeplasma laidlawii. Journal of General Virology 12, 65-67. || 34. (1972). Isolation and characterisation of mycoplasma viruses. In PathougaisilyssmlásmIla Ciba Foundation Symposium. Amsterdam. ASP. 145-156. || 35. 4.11 GARWES, D. J., BRUCF J. & WYLD, S. G. (1973). Further studies on the morphology and composition of Mycoplasmatales virus - laidlawii 45 2. Journal of General Virolooy 18, 127-133. || 36. & WYLD, S. G. (1973). Isolation of Mycoplasmatales virus laidlawii 3, a new virus infecting Acholeolasma laidlawii. Journal of General Virology (in press)

Extracting partition statistics from semistructured data

The effective grouping, or partitioning, of semistructured data is of fundamental importance when providing support for queries. Partitions allow items within the data set that share common structural properties to be identified efficiently. This allows queries that make use of these properties, such as branching path expressions, to be accelerated. Here, we evaluate the effectiveness of several partitioning techniques by establishing the number of partitions that each scheme can identify over a given data set. In particular, we explore the use of parameterised indexes, based upon the notion of forward and backward bisimilarity, as a means of partitioning semistructured data; demonstrating that even restricted instances of such indexes can be used to identify the majority of relevant partitions in the data

Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling

Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their translocation to the nucleus, where they regulate gene expression. BMPs can also signal independently of SMAD4, but this pathway is poorly understood. Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. We also demonstrate that PAWS1 regulates the expression of several non-BMP target genes, suggesting roles for PAWS1 beyond the BMP pathway

Unanchored tri-NEDD8 inhibits PARP-1 to protect from oxidative stress-induced cell death

NEDD8 is a ubiquitin‐like protein that activates cullin‐RING E3 ubiquitin ligases (CRLs). Here, we identify a novel role for NEDD8 in regulating the activity of poly(ADP‐ribose) polymerase 1 (PARP‐1) in response to oxidative stress. We show that treatment of cells with H2O2 results in the accumulation of NEDD8 chains, likely by directly inhibiting the deneddylase NEDP1. One chain type, an unanchored NEDD8 trimer, specifically bound to the second zinc finger domain of PARP‐1 and attenuated its activation. In cells in which Nedp1 is deleted, large amounts of tri‐NEDD8 constitutively form, resulting in inhibition of PARP‐1 and protection from PARP‐1‐dependent cell death. Surprisingly, these NEDD8 trimers are additionally acetylated, as shown by mass spectrometry analysis, and their binding to PARP‐1 is reduced by the overexpression of histone de‐acetylases, which rescues PARP‐1 activation. Our data suggest that trimeric, acetylated NEDD8 attenuates PARP‐1 activation after oxidative stress, likely to delay the initiation of PARP‐1‐dependent cell death

Adult nurse turnover and retention : South London project report

This project was commissioned by Health Education South London (HESL) in response to the workforce planning process for 2014/15 indicating an unprecedented increase in demand for adult nurses in NHS Trusts. The focus of the project was to identify issues and interventions to improve retention of adult nurses and reduce the rate of leaving jobs (turnover). During 2015 the work of the project has included: a systematic literature review to examine evidence of determinants, costs and interventions of adult nurse turnover; analysis of adult nurse workforce data to identify trends and rates in sub-groups of nurses and by characteristics of their employment context; interviews with senior nurse and human resource managers across South London for views and examples of initiatives to reduce turnover; interviews with adult nurses and nurse managers managers as to their views on the issues and initiatives that might help retain nurses. The evidence from each element is presented and then synthesised

What aspects of intentional rounding work in hospital wards, for whom and in what circumstances? A realist evaluation protocol

INTRODUCTION: Intentional rounding (IR) is a structured process whereby nurses in hospitals carry out regular checks, usually hourly, with individual patients using a standardised protocol to address issues of positioning, pain, personal needs and placement of items. The widespread implementation of IR across the UK has been driven by the recommendations of the Francis Inquiry although empirical evidence of its effectiveness is poor. This paper presents a protocol of a multimethod study using a realist evaluation approach to investigate the impact and effectiveness of IR in hospital wards on the organisation, delivery and experience of care from the perspective of patients, their family members and staff. METHODS AND ANALYSIS: The study will be conducted in four phases. Phase 1: theory development using realist synthesis to generate hypotheses about what the mechanisms of IR may be, what particular groups may benefit most or least and what contextual factors might be important to its success or failure which will be tested in subsequent phases of the study. Phase 2: a national survey of all NHS acute trusts to explore how IR is implemented and supported across England. Phase 3: case studies to explore how IR is implemented 'on the ground', including individual interviews with patients, family members and staff, non-participant observation, retrieval of routinely collected patient outcomes and cost analysis. Phase 4: accumulative data analysis across the phases to scrutinise data for patterns of congruence and discordance and develop an overall evaluation of what aspects of IR work, for whom and in what circumstances. ETHICS AND DISSEMINATION: The study has been approved by NHS South East Coast-Surrey Research Ethics Committee. Findings will be published in a wide range of outputs targeted at key audiences, including patient and carer organisations, nursing staff and healthcare managers

Bone Density Screening and Re-screening in Postmenopausal Women and Older Men

Clinical practice guidelines universally recommend bone mineral density (BMD) screening to identify osteoporosis in women aged 65 years and older. Risk assessment is recommended to guide BMD screening in postmenopausal women under age 65. Insufficient data are available to inform standard ages to start and stop BMD screening in postmenopausal women. Based on longitudinal studies of incident osteoporosis and fracture in postmenopausal women, an initial BMD test should be ordered for all women aged 65, and the frequency of re-screening should be based on age and BMD T score (more frequent testing for older age and lower T score). Although clinical practice guidelines recommend BMD screening according to risk factors for fracture in postmenopausal women under age 65, no standard approach to risk assessment exists. Minimal evidence is available to guide osteoporosis screening in men, but some experts recommend initiation of BMD screening in men at age 70