A review of risk factors for bovine tuberculosis infection in cattle in the UK and Ireland.

Bovine tuberculosis (bTB) is an important disease of cattle caused by infection with Mycobacterium bovis, a pathogen that may be extremely difficult to eradicate in the presence of a true wildlife reservoir. Our objective was to identify and review relevant literature and provide a succinct summary of current knowledge of risk factors for transmission of infection of cattle. Search strings were developed to identify publications from electronic databases to February 2015. Abstracts of 4255 papers identified were reviewed by three reviewers to determine whether the entire article was likely to contain relevant information. Risk factors could be broadly grouped as follows: animal (including nutrition and genetics), herd (including bTB and testing history), environment, wildlife and social factors. Many risk factors are inter-related and study designs often do not enable differentiation between cause and consequence of infection. Despite differences in study design and location, some risk factors are consistently identified, e.g. herd size, bTB history, presence of infected wildlife, whereas the evidence for others is less consistent and coherent, e.g. nutrition, local cattle movements. We have identified knowledge gaps where further research may result in an improved understanding of bTB transmission dynamics. The application of targeted, multifactorial disease control regimens that address a range of risk factors simultaneously is likely to be a key to effective, evidence-informed control strategies.

The effects of a kinin antagonist on changes in lung function and plasma extravasation into the airways following challenge of sensitized guinea-pigs.

BACKGROUND: It has been suggested that kinins may play a role in allergic pathophysiology of the airways, contributing to bronchoconstriction and oedema formation. Raised levels of kinin generating enzymes and kinins are found in the airways during allergic responses. OBJECTIVE: Using an in vivo animal model of allergen induced increase in airways resistance we investigated the effects of the bradykinin antagonist Hoe 140, in order to assess the possible contribution of kinins to this response. METHODS: Guinea-pigs were sensitized and challenged with ovalbumin (OA) or saline via the endotracheal route and the resulting increase in airways resistance was measured by whole body plethysmography. At 240 min after challenge, bronchoalveolar lavage fluid (BALF) was taken and albumin content and kallikrein-like activity determined by rocket immunoelectrophoresis and use of artificial substrates respectively. Pretreatment of animals with the bradykinin antagonist Hoe 140 at 6.7, 20 or 66.7 nmol/kg or aprotinin (46,000 kallikrein inhibitor units/kg) was by i.p. injection 10 min before challenge. RESULTS: Pre-treatment with Hoe 140 dose dependently attenuated the increase in airways resistance following allergen challenge. Kallikrein-like activity and albumin in BALF were unaltered. Aprotinin reduced the kallikrein-like activity in BALF but did not alter airways resistance. CONCLUSION: Kinins may contribute to a significant part of allergen-induced airways resistance increase in this model but not via an effect on plasma extravasation.

Mechanism of irritant-induced cough: studies with a kinin antagonist and a kallikrein inhibitor.

It has been suggested that bradykinin may play a role in stimulating cough in at least one pathological condition in humans. We have employed an animal model to investigate the possible role of this peptide in irritant-induced cough. The kinin antagonist Hoe 140 and codeine both produced dose-related inhibition of cough responses to inhalation of citric acid or bradykinin aerosols by conscious guinea pigs. The selective tissue kallikrein inhibitor CH694 inhibited cough caused by citric acid but not by bradykinin. Indomethacin pretreatment attenuated the responses to both stimuli as did phosphoramidon. It is concluded that cough produced by citric acid inhalation may be mediated, at least in part, by generation of kinins; secondary to this, a release of prostanoids also appears to participate in the response.

Urinary excretion of thyroid hormones in rainbow trout, Oncorhynchus mykiss.

Urinary excretion of the thyroid hormones (TH) L-thyroxine (T4), and 3,5,3'-triiodo-L-thyronine (T3) and their derivatives was studied in urinary-catheterized rainbow trout (mean wt. 227 g) fasted for 2 days under a 12-hr L:12-hr D photocycle in running water (12 degrees). Catheterized trout were intracardiac-injected with [125I]T4 (*T4) or [125I]T3 (*T3) and urine was collected as 2-hr fractions over 48 hr. The 125I corresponding to I-, TH conjugates (sulfates and glucuronides), or TH was separated by LH-20 column chromatography and HPLC. Urine production (daily mean, 72.5 ml/kg/day) was lowest during the scotophase and doubled at the start of photophase, causing acute fluctuations in excretion of 125I-labeled materials, and implying dependence on glomerular filtration rate. During the first 48 hr, 8.2% of *T4 (I-, 3.6%: TH conjugates, 1.7%; TH, 2.9%) and 6.7% of injected *T3 (I-, 1.8%; TH conjugates, 2.5%; TH, 2.4%) was excreted in urine; 32.6% (*T4) and 26.4% (*T3) was in the gall bladder; 45.5% (*T4) and 45.7% (*T3) were in the remaining carcass; and 13.7% (*T4) and 23.7% (*T3) were lost via other routes. We extrapolate that about 15% of *T4-injected and 12% of *T3-injected total radioactivity would be excreted ultimately in urine, with 8.4% (*T4) and 9.0% (*T3) as TH or their conjugates. Neither a T4 nor a T3 challenge (20 ng/g) influenced the amount of radioactive loss in urine over 48 hr. We conclude that the urine is a significant route for excretion of TH and their conjugates, and that urinary TH loss depends to a large extent on the rate of urine production.

Kallikrein-like activity in the bronchoalveolar lavage (BAL) fluid of sensitized, challenged guinea-pigs.

Sensitization and challenge of guinea-pig airways with aerosols of ovalbumin solution administered through an endotracheal tube leads to a significant increase in kallikrein-like enzyme activity in bronchoalveolar lavage (BAL) fluid. This increase is present up to six hours after challenge and may be related to changes in airways resistance that persist for similar periods.

Measurement of surface antigen by specific bacterial adherence and scanning electron microscopy (SABA/SEM) in cells infected by vesiculovirus ts mutants.

Temperature-sensitive (ts) mutants of the rhabdoviruses vesicular stomatitis virus and Chandipura virus have been used to measure the appearance of virus antigen on the surface of infected cells by the technique of surface analysis by bacterial adherence and scanning electron microscopy (SABA/SEM). The number of staphylococci specifically adhering to antiserum-treated infected PTK-2 or BSC-1 cells at permissive (31 degrees C) and restrictive (39 degrees C) temperatures was followed in time-course experiments and a close correspondence was observed between the proportion of staphylococci bound at 39 degrees C and the known phenotypic properties of the ts mutants. Virus surface antigen was undetected in cells infected by transcription- and replication-defective ts mutants with thermolabile L proteins under restrictive conditions up to an input multiplicity of infection of 50, and in cells infected by a replication-defective NS protein mutant. Some surface antigen was detected late in infection in PTK-2 cells infected by a replication-defective N protein mutant. Surface antigen accumulated normally in maturation-defective mutants with lesions in envelope proteins. These results establish the suitability of the SABA/SEM technique for quantitative estimation of virus antigen on the surface of infected cells.

Examination of different preparations of human placental plasma membrane for the binding of insulin, transferrin and immunoglobulins.

Plasma membrane was prepared from human placental tissue by two standard methods. The preparations, termed PVM and PPM, examined by electron microscopy and polyacrylamide gel electrophoresis, were characterized with respect to their binding properties for insulin, transferrin, alpha 2-macroglobulin and the immunoglobulins, IgM and IgG1. By means of sucrose density-gradient centrifugation, it was possible to fractionate the PVM into two distinct fractions. The first fraction, under the conditions used, was heavier (density greater than 1.080 g . cm-3) and was obtained as a pellet. It bound transferrin and IgM and had low specific activities for 5'-nucleotidase and for the binding of IgG1. The lighter fraction (density range 1.048-1.050 g . cm-3) had a high specific activity for 5'-nucleotidase and for IgG1 binding. Transferrin and IgM did not bind to this fraction. Insulin bound to both the fractions with comparable levels of specific binding activity, while alpha 2-macroglobulin binding was undetectable. The PPM preparation was found to have binding properties similar to those of the light fraction of PVM.

Pneumoviruses: the cell surface of lytically and persistently infected cells.

Human embryonic lung (MRC-5), feline embryo (FEA), mink lung (Mv1Lu) and monkey kidney (BSC-1) cells infected by respiratory syncytial virus showed characteristic morphological changes when viewed by scanning electron microscopy. The surfaces of respiratory syncytial virus-infected cells developed a profusion of slender filaments after 48 h incubation at 31 degrees C. Similar changes in surface morphology were observed in BSC-1 cells infected by murine pneumonia virus. Filament production therefore appears to be a common property of pneumo-viruses. Filaments were not observed in cells infected with either syncytial and non-syncytial herpes simplex virus, the cytocidal vesicular stomatitis and Batai (Bunyaviridae) viruses, or the focus-inducing rabbit fibroma virus. Filament production was not observed in cells infected with ts mutants of respiratory syncytial (RS) virus during incubation at the restrictive temperature, or in a persistently infected culture of BSC-1 cells at 37 degrees C. The persistently infected cells (the RS ts 1/BSC-1 line) had some of the characteristics of cells transformed by oncogenic viruses, namely ability to overlap adjacent cells and agglutination by a low concentration of concanavalin A. The pseudo-transformed phenotype was temperature-dependent, however, and suppressed by raising the temperature of incubation to 39 degrees C. The presence of virus antigen at the cell surface was similarly temperature-dependent in these cells, diminished at high temperature (39 degrees C) and enhanced at low temperature (31 degrees C), suggesting that the changes in the host cell were the result of insertion of virus protein into the cell membrane. Evidently, persistent infection by a cytoplasmic virus can produce alterations in the host cell usually associated with transformation by nuclear viruses.