Isolation of Brucella species from common seals in Northern Ireland.
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Animals↗
Biomedical subjects
C R Watson
Publications and source records attributed to C R Watson.
International radiobiology archives of long-term animal studies: structure, possible uses and potential extension.
Animal experiments have contributed a great deal to our information on effects and risks arising from exposure to radionuclides. This applies, in particular, to alpha-emitting radionuclides where information from man is limited to thorotrast, 224Ra and 226Ra. The late C.W. Mays was the first to suggest that animal data in conjunction with epidemiological data could allow estimates of human risks for radionuclides - predominantly from actinides - where information in man is scarce. The 'International Radiobiology Archives of Long-term Animal Studies' were created through the combined efforts of European, American and Japanese scientists and aim to safeguard the large amount of existing data on long-term animal experiments and make them available for, among others, an improved assessment of risks from alpha-emitting radionuclides. This paper summarizes the structure of the archives and reviews their present status and future plans. It also demonstrates the extensive information available in these archives on alpha-emitting radionuclides which is suitable for further analysis. Also, the structure of the animal archives could - in a slightly modified form - accommodate the epidemiological data available on 224Ra and thorotrast and, thus, facilitate a direct comparison of data from man, dogs and rodents.
Animals↗
K-ras mutations in 239PuO2 canine lung neoplasms.
Single-strand conformational polymorphism (SSCP) analysis and direct sequencing methods were used to examine lung tumors derived from a cohort of beagle dogs with inhalational exposures to 239PuO2. These exposures were done at Pacific Northwest Laboratories where 18-month-old beagle dogs were given 239PuO2 by single-dose inhalation and allowed to live out their life-spans. Formalin-fixed paraffin-embedded blocks of tissues from 25 dogs exposed to 239PuO2 by aerosol inhalation which later developed lung tumors were available for this study. Two of 25 tumors had mutations within exon 1 of K-ras detected by SSCP analysis. Both mutations were GGT to GAT transitions at codon 12 confirmed by direct sequencing experiments. One was an adenocarcinoma from the medium-high exposure group and the other was a broncheolo-alveolar carcinoma from the medium-low exposure group. The rate of K-ras mutations in plutonium-induced lung tumors described herein (8%) was greater than previously described in canine plutonium-induced lung tumors (0%), but was less than that which we have described in spontaneous canine lung cancer (16%), less than that reported for human spontaneous non-small cell lung cancer (13-36%) and less than that described in rats with spontaneous lung cancer (40%) or lung tumors following 239Pu inhalation exposure (46%).
Administration, Inhalation↗
Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2.
Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets.
Administration, Inhalation↗
New guidelines for management and prevention of meningococcal disease in Australia. Meningococcal Disease Working Party of the National Health and Medical Research Council.
The incidence of invasive meningococcal disease in Australia has increased over the past decade, and in April 1997 the National Health and Medical Research Council published guidelines for management of patients with meningococcal disease and their contacts. These guidelines emphasise the need for immediate intravenous antibiotic treatment of patients with suspected meningococcal disease, before transfer to hospital or lumbar puncture. When possible, blood for culture should be collected before antibiotic therapy, if this does not delay treatment.
Adolescent↗
Biological effects of inhaled 238PuO2 in beagles.
Beagle dogs exposed to 238PuO2 aerosols (136 dogs, 13-22 per group, mean initial lung depositions of 0.0, 0.13, 0.68, 3.1, 13, 52 and 210 kBq) were observed throughout life to determine tissues at risk and dose-effect relationships. The pulmonary retention of 238Pu was represented by the sum of two exponentially decreasing components of the initial lung deposition; about 84% cleared with a 174-day half-time; the half-time of the remainder was 908 days. The average percentages of final body burden found in lung, skeleton, liver and thoracic lymph nodes in the 30 longest-surviving dogs (mean survival 14 years) were 1, 46, 42 and 6%, respectively. Of 116 beagles exposed to plutonium, 34 (29%) developed bone tumors, 31 (27%) developed lung tumors, and 8 (7%) developed liver tumors. Although lungs accumulated a higher average radiation dose than skeleton, more deaths were due to bone tumors than to lung tumors. Deterministic effects included radiation pneumonitis, osteodystrophy, hepatic nodular hyperplasia, lymphopenia, neutropenia and sclerosing tracheobronchial lymphadenitis. Hypoadrenocorticism was also observed in a few dogs. Increased serum alanine aminotransferase, indicative of liver damage, was observed in groups with > or =3.1 kBq initial lung deposition. Estimates of cumulative tissue dose in a human exposed to airborne 238PuO2 for 50 years at a rate of one annual limit on intake each year were derived based on a comparison of the data on metabolism for humans and beagles. The 50-year dose estimates for humans are an order of magnitude lower than doses at which increased incidence of neoplasia was observed in these dogs, whereas the projected doses to humans from 50-year exposure at the annual limit of intake are of similar magnitude to those at which deterministic effects were seen in the beagles.
Addison Disease↗
The distribution and effects of inhaled 239Pu(NO3)4 deposited in the liver of dogs.
The distribution and effects of inhaled 239Pu(NO3)4 deposited in the liver of dogs were studied in five groups of 20 beagles exposed to initial lung depositions ranging from 1.0 to 520 Bq g(-1) lung. Following life-span observations, the liver contained 40 +/- 1% of the final body deposition of plutonium, second only to the skeleton. The liver-to-skeleton ratio of deposited plutonium for total organ was 0.8, or 3.5 when expressed on a per-gram basis. There was no effect of exposure level on liver-to-skeleton ratios. Autoradiographs showed that the dose rate delivered to parenchymal cells was higher than evident from radiochemical analysis of the whole organ. Elevated levels of serum liver enzymes were observed in groups with mean liver concentrations of 1.3 Bq g(-1) and liver doses of 3 Gy or higher. Nodular hyperplasia of liver and bile-duct hyperplasia were observed. Liver tumors, principally of bile-duct epithelium, were late-occurring and were observed at lower exposure levels at which life span was not shortened by lung or bone tumors.
Aerosols↗
Hypoadrenocorticism in beagles exposed to aerosols of plutonium-238 dioxide by inhalation.
Hypoadrenocorticism, known as Addison's disease in humans, was diagnosed in six beagles after inhalation of at least 1.7 kBq/g lung of 238PuO2. Histological examination of adrenal gland specimens obtained at necropsy revealed marked adrenal cortical atrophy in all cases. Autoradiographs showed only slight alpha-particle activity. Although the pathogenesis of adrenal cortical atrophy in these dogs is unclear, there is evidence to suggest an autoimmune disorder linked to damage resulting from alpha-particle irradiation to the lymphatic system.
Addison Disease↗
Medical misadventure, indemnity and public health.
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Australia↗
Familial influence on plaque formation in the beagle brain.
Aged canines exhibit central neuropathological changes strikingly similar to those seen in patients with Alzheimer's disease. In this study, brain tissue from pure bred beagles raised in a controlled environment were examined for Alzheimer-like pathology. The mean age of the animals was 15.6 years. The incidence of plaques among these 29 dogs was 65.5%. Of the 19 samples that demonstrated Alzheimer-like pathology, 18 were characterized as diffuse and one as neuritic. Plaque density was found to be independent of age. Plaque numbers were highest in the perirhinal cortex and the adjacent temporal cortex. Familial influence on plaque development is supported by congruence within 15 of the 16 litters examined (p < 0.001). In this environmentally controlled group the diffuse plaques were rarely converted to the dense neuritic plaques found in Alzheimer's disease.
Aging↗
Organization of the olivocerebellar projection in the rat.
The olivocerebellar projection has been studied in the rat using the horseradish peroxidase (HRP) retrograde tracing technique. All regions of the cerebellum, except for the flocculonodular lobe, were injected with small volumes of HRP. The overall organization of the rat olivocerebellar projection is similar in all major respects to that found in other mammals. For example, in the rat Crus 1 and Crus 2 receive afferents from the principal olive, medial part of the rostral dorsal olive, the rostral medial olive, the dorsal cap and the ventrolateral outgrowth which agrees with studies in the cat. The most notable difference between the present study and studies in other mammals is the finding of a projection in the rat from the dorsomedial cell column to all regions of the cerebellar hemispheres, except for the paraflocculus.
Animals↗
The development of facial motoneurones in the mouse--neuronal death and the innervation of the facial muscles.
The relationship between neuronal death and the formation of patterned connections was studied in the facial neuromuscular system of foetal, neonatal, and adult mice. The facial neuromuscular system was selected because two large, widely separated, facial muscles (the nasolabial and posterior auricular muscles) are innervated by clearly separated parts of the facial motor nucleus in the adult mouse. The number of motorneurones in the facial nucleus was counted in Nissl-stained sections at different stages of development. Over 6400 neurones were present in the facial nucleus at day 17 p.c. (post-coitum). After day 17 p.c. the number of neurones fell rapidly and only 2000 cells remain in the adult nucleus. This represents a loss of 68%, most of which occurs between days 18 and 20 p.c. Neurones with pyknotic nuclei are seen on day 17 p.c. and are most numerous on day 18 p.c. This leads us to believe that the fall in neurone numbers is due to cell death. Indirect evidence provided by acetylcholinesterase histochemistry (time of earliest reaction in the facial muscles) and horseradish peroxide (HRP) tracing studies (time of earliest transport) indicate that facial motorneurone axons innervate the facial musculature before the period of cell death: diffuse acetylcholinesterase activity first appeared in the auricular muscles at day 15 p.c. and in the nasolabial muscles at day 17 p.c.; retrograde transport of HRP from the auricular and nasolabial muscles to the facial nucleus cannot be reliably demonstrated before day 17 p.c. We assessed the topography of early facial neuromuscular innervation by making HRP injections into nasolabial and posterior auricular muscles of embryonic and neonatal mice. Injections of HRP at day 17 p.c. (the day before cell loss commenced) showed that the nasolabial muscle and posterior auricular muscles were innervated by the same subnuclei of the facial nucleus as in the adult--except that there was a small number (1-5%) of labelled cells located in parts of the nucleus not consistent with the adult innervation pattern. These data indicate that, except for a small number of neurones, topographically organized connections in the facial neuromuscular system are established before the period of cell death. We conclude that motoneurone cell death does not play a major role in the establishment of topographically organized connections in this system.
Acetylcholinesterase↗
Organization of the facial nucleus in the rat.
The topographic organization of the facial nucleus motoneurons in the rat was investigated with the horseradish peroxidase retrograde tracing method using tetramethyl benzidine as a chromogen. Facial muscles were 'represented' on the facial nucleus in an orderly fashion. For example, the motoneurons supplying the rostral (nasolabial) muscles are laterally placed, whereas those supplying the caudal (auricular) muscles are medially placed. Notable findings in this study are: (i) the relatively unremarkable size of the nasolabial (vibrissal) muscle representation; there does not seem to be an increase in size of this part of the nucleus, commensurate with the specialized sensory functions of the vibrissal area of the face and (ii) the neurons supplying the posterior belly of the digastric are found in the suprafacial nucleus which lies about 1 mm dorsal to the main facial nucleus.
Animals↗
The distribution of ipsilaterally and contralaterally projecting ganglion cells in the retina of the pigmented rabbit.
The retinal distribution of ipsilaterally and contralaterally projecting ganglion cells has been determined in the rabbit using both degeneration and horseradish peroxidase tracing techniques. Contralaterally projecting ganglion cells are present throughout the retinas, while ipsilaterally projecting ganglion cells are confined to a 3.0-3.5 mm wide strip adjacent to the temporal retinal margin. Thus, in this temporal strip both ipsilaterally and contralaterally projecting cells intermingle, while at more nasal locations all ganglion cells project contralaterally. Each of the contra- and ipsilaterally projecting populations comprises ganglion cells with soma diameters representing the full range present in the rabbit retina. However, a relatively large proportion of the ipsilaterally projecting ganglion cells have large somata (greater than or equal to 20 micrometer). Large ganglion cells are most numerous in the rabbit's temporal retina and have previously been described as reaching their peak density at the large cell node, just above the temporal end of the visual streak (Provis 1979). The large cell node lies immediately temporal to the nasal border of the strip of retina in which ipsilaterally projecting cells are located. It is possible that this specialization in the region of retina which observes the binocular visual field plays a particular role in binocular vision for the rabbit.
Afferent Pathways↗
Microfiche-based exercise in clinical microbiology--a valuable assessment technique for teachers and students.
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Education, Medical, Undergraduate↗
Gradients between nasal and temporal areas of the cat retina in the properties of retinal ganglion cells.
Evidence is presented of gradients between nasal and temporal areas of the cat's retina in the properties of their ganglion cell populations. Mean ganglion cell size is greater in temporal retina than in nasal retina, partly because the alpha- and beta-cells of temporal retina are distinctly bigger than their counterparts in nasal retina, and partly because more medium-sized cells, and fewer small cells, are to be found in temporal retina. This high proportion of medium-sized ganglion cells may reflect a high proportion of beta-cells or of the medium sized gamma-cells described by Stone and Clarke ('80). Several of these differences can be related to prior morphological, electrophysiological, and behavioural observations in the cat, and similar differences have been reported in several other mammalian species. Evidence is presented that, in the cat, at least some of these differences are less marked near the vertical meridian of the retina than more temporally or nasally. The present results may therefore, be evidence of a nasal-temporal gradient in retinal structure and funtion common to many mammals, and distinct from previously recognised gradients in ganglion cell properties related to the area centralis and visual streak specialisations.
Animals↗
AChE-stained horizontal sections of the rat brain in stereotaxic coordinates.
This paper presents an atlas of the rat brain based on horizontal sections stained for acetylcholinesterase (AChE). Fourteen labeled photographs from sections at 0.5 mm intervals are presented. The atlas is intended for use with male rats 250-300 g in weight. It was constructed using the flat-skull position (lambda and bregma in same horizontal plane). Either the interaural midline or bregma can serve as the reference zero point. We have found the stain for AChE to be a useful general purpose stain for identifying brain nuclei and tracts.
Acetylcholinesterase↗