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Biomedical subjects

M M Cooke

Publications and source records attributed to M M Cooke.

At least 19 recordsLinked to original sources
PubMed2003

Experimental infection with BCG as a model of tuberculosis in the brushtail possum (Trichosurus vulpecula).

AIMS: To study the development and progression of lesions produced following experimental inoculations of possums with Bacille Calmette-Guérin (BCG) Pasteur Strain 1173P2 and to compare these with lesions that occurred following natural Mycobacterium bovis infection. METHODS: Possums were inoculated with 5 x 106 colony forming units (cfu) of BCG via the intra-dermal (I/D) route into the dorsum of the neck (n=38) or the left brachium (n=7),orally (n=10), via the endobronchial (E/B) route (n=12), or intravenously (I/V) (n=10, half of which received 5 x 106 cfu and half of which received 5 x 107 cfu of BCG). The possums were humanely killed between 1-4 weeks post inoculation (p.i.), and the nature and distribution of lesions examined grossly and histopathologically. RESULTS: The distribution of lesions following I/D inoculation via either route was similar to that of the natural disease, but there were few lesions in the lung. Endobronchial inoculation resulted in pulmonary disease but produced few lesions outside the respiratory tract. Lesions produced by I/V inoculation were similar in distribution to those seen in terminally ill tuberculous possums. No lesions were produced following oral inoculation. Regression of lesions commenced after 3 weeks p.i. CONCLUSIONS: Although the phenomenon of lesion resolution restricts the use of BCG to the study of early lesion development, it avoids the overwhelming disease induced using M. bovis and thus allows the early phases of the development and progression of tuberculosis in this species to be observed. Intradermal inoculation produced evidence that infection through the skin is associated with lesions in superficial lymph nodes, whereas pulmonary disease was associated with E/B inoculation. The results are consistent with the hypothesis that both percutaneous and respiratory routes are important in natural infection of possums with M. bovis.

Journal Article↗
PubMed2002

Accidental Mycobacterium bovis infection in a veterinarian.

CASE: A veterinarian developed tenosynovitis and secondary carpal tunnel syndrome following accidental inoculation of Mycobacterium bovis during the necropsy of a tuberculous possum from Westland, New Zealand. CLINICAL RELEVANCE: M. bovis infection is a zoonotic disease, and occupational exposure to tuberculous animals places people at risk of contracting the disease. CONCLUSIONS: Adhering to safe work practices reviewed in this article is important to minimise the risk of infection to people handling tuberculous animals.

Journal Article↗
PubMed2001

Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines.

Radiographic mammary microcalcifications are one of the most pertinent diagnostic markers of breast cancer. Breast tissue calcification in the form of calcium hydroxyapatite (HA) is strongly associated with malignant disease. We tested the hypothesis that calcium HA may exert biological effects on surrounding cells, thereby facilitating breast cancer progression. Our findings showed that HA crystals enhanced mitogenesis in breast cancer cell lines MCF-7 and Hs578T and also in normal human mammary epithelial cells. HA crystals were also found to upregulate the production of a variety of matrix metalloproteinases (MMPs), including MMP-2, -9, and -13 in MCF-7 and MMP-9 in human mammary epithelial cell lines. HA crystals were found to greatly augment prostaglandin E(2) levels in Hs578T cells, and treatment with a cyclooxygenase inhibitor, aspirin, abrogated the HA-induced mitogenesis. These results suggest that calcium HA crystals may play an active role in amplifying the pathological process involved in breast cancer.

Breast Neoplasms↗
PubMed2001

Mycobacterium bovis infection in wildlife in New Zealand.

Bovine tuberculosis (Tb) is the most important disease of livestock in New Zealand, and it puts at risk the nation's trade in dairy, beef and venison products. Elimination of the disease from livestock is based on a herd test and slaughter programme and carcass inspection at abbatoirs. However, this programme has not been as successful as expected, because the disease also occurs in wild or feral animals acting as vectors of the disease to livestock. Brushtail possums are the major wildlife vector and self-sustaining maintenance host of Tb, and play a role analogous to that of the badger in Great Britain. In contrast, some deer species and ferrets may act as vectors of the disease, but their role in transmitting Tb to livestock is unclear. Hedgehogs, pigs, cats, sheep and goats are now considered to be amplifier hosts, and spread the disease to other species only when inspected or their carcasses scavenged. In the absence of infected possum populations, these species do not appear to be capable of maintaining the infection in their own populations and are not thought to be involved in the maintenance of Tb in livestock. Tuberculosis has also been recorded from stoats, hares, and a rabbit, but the level of infection recorded in their populations indicates these species are unlikely to spread the disease to other animals and hence are not involved in the transmission of Tb to livestock.

Animals↗
PubMed2000

A neurological syndrome in a free-living population of possums (Trichosurus vulpecula).

AIMS: To determine the clinical and pathological features of a neurological disease syndrome in a free-living possum population in New Zealand and to compare this syndrome with wobbly possum disease. METHODS: An outbreak of a neurological disease in possums in the Rotorua district was investigated in 1994. A variety of tissues was collected and investigated microbiologically and histopathologically. Tissues stored from clinically affected possums were homogenised, clarified and inoculated into healthy possums by the intra-peritoneal route. The clinical signs and histopathological lesions in naturally-infected and in experimentally-inoculated possums were assessed and compared with those of possums affected with wobbly possum disease. RESULTS: Histopathological investigation of three of the naturally-affected possums revealed non-suppurative encephalitis with perivascular cuffing, diffuse non-suppurative meningitis and focal non-suppurative myocarditis. These lesions were suggestive of a viral infection. No pathogenic bacteria were recovered and no viruses were isolated in tissue culture. A neurological disease, indistinguishable from wobbly possum disease, was reproduced in five out of the eight experimentally inoculated possums. In two experimental cases the clinical signs were very mild and, in most cases of the natural and experimental disease, histopathological lesions in the central nervous system were mild in comparison with wobbly possum disease. Possums which did not develop clinical signs of neurological disease or have lesions in the central nervous system did have infiltrations of mononuclear inflammatory cells in the liver and kidney. CONCLUSIONS: This neurological disease, reported for the first time in a free-living population, closely resembles and may be the same as wobbly possum disease. The milder nature of this disease could suggest there may be more than one strain of the aetiological agent.

Journal Article↗
PubMed1999

Temporal patterns in bovine tuberculosis in a brushtail possum population contiguous with infected cattle in the Ahaura Valley, Westland.

AIMS: To determine temporal and spatial patterns of bovine tuberculosis (Tb) in a population of brushtail possums (Trichosurus vulpecula) free from commercial and recreational hunting and living contiguously with livestock, and to relate these patterns to measures of possum health and density. METHODS: Possums were trapped on 11 lines located on a forest-rough grazing margin in the Ahaura Valley in Westland in 1979-80 and each August from 1992 to 1996, and were examined post mortem for gross lesions indicative of Tb. Infection levels in possums were compared with Th test data from cattle grazing in the same area. RESULTS: Tuberculosis was identified from the trapped sample of possums in 1980. Trapping of further possums on the same trap lines confirmed the presence of the disease each year from 1992 to 1996, and suggested a clustering of infection in time and space. The prevalence of Tb in possums declined with increasing possum population size and well being, and decreasing age. The prevalence of Tb in possums was highest in 1980 and 1992, and appeared to roughly coincide with similar upsurges in Tb in nearby cattle. CONCLUSIONS: Our results suggest that the exceptional levels of Tb recorded in possums in 1992 had a direct effect on possum numbers, and gave rise to very low trap catches in 1993-94. They also suggest that Tb can persist for several years in possum populations existing well below the 5% trap catch targeted by regional councils for Tb possum control.

Journal Article↗
PubMed1999

The pathogenesis of experimental endo-bronchial Mycobacterium bovis infection in brushtail possums (Trichosurus vulpecula).

AIM: To study the nature and development of experimentally induced respiratory tuberculosis in possums and compare the lesions observed with those seen in the natural disease. METHODS: Thirty-three adult possums were inoculated via the endo-bronchial route with 20-100 colony forming units of Mycobacterium bovis. The possums were killed at 1,2,3 and 4 weeks after inoculation and the nature and distribution of the lesions studied in detail histopathologically. Alveolar macrophages recovered from the infected possums were also studied ultrastructurally. RESULTS: Macroscopic lesions were largely confined to the respiratory tract, increasing in size and number with time. Histology greatly increased the detection of the total number of lesions. The most common sites affected outside the respiratory tract were the liver and hepatic lymph nodes, but lesions were less common in peripheral lymph nodes than is observed in the natural disease. Intra-pulmonary lesions were centred on blood vessels and their associated lymphatics. Peripheral blood lymphocyte blastogenic responses to M. bovis antigens were first detected at 3 weeks after inoculation, which was 1 week after lymphocyte infiltrations were detected in the lungs, but 1 week before the majority of infections became generalised. CONCLUSIONS: Differences in the nature of pulmonary lesions and the distribution of lesions were observed between experimentally induced and the natural disease. Rapid haematogenous and lymphatic spread occurs early in the experimentally induced disease.

Journal Article↗
PubMed1995

Naturally occurring tuberculosis caused by Mycobacterium bovis in brushtail possums (Trichosurus vulpecula): I. An epidemiological analysis of lesion distribution.

Gross and microscopic lesion distributions and culture test results are described for 73 tuberculous possums recovered from a series of cross-sectional studies involving about 500 detailed necropsies. Pathological findings from 11 terminally ill tuberculous possums are also described. Quantitative epidemiological techniques were applied to lesion site data to assess factors influencing the pathogenesis of the disease. In possums with gross lesions, the number of distinct body sites affected varied from one to 10 per animal, with a mean of 4.6. The total number of gross plus microscopic lesions varied from one to 28 per animal with a mean of 11.6, indicating that the degree of generalisation of disease was much greater than appeared grossly. Of 119 possums with no gross lesions which were subjected to additional examinations, tuberculosis was diagnosed in ten (8.4%) by histology or culture of pooled lymph nodes. Among cross-sectional sample tuberculous possums, lesions were found in lungs in 85%, in axillary lymphocentres in 85%, in inguinal lymphocentres in 69%, and in either axillary or inguinal lymphocentres in 95%, indicating that the disease spread rapidly to multiple body sites. More males than females were infected (relative risk = 1.78). When cross-sectionally sampled infected and non-infected possums were compared, no significant associations were found between the presence/absence of disease and either age or indices of body condition, although debility was seen in animals with terminal illness.

Journal Article↗
PubMed1995

Naturally occurring tuberculosis caused by Mycobacterium bovis in brushtail possums (Trichosurus vulpecula): II. Pathology.

The gross and microscopic lesions due to Mycobacterium bovis infection are described in 73 brushtail possums (Trichosurus vulpeculu) from population studies and from 11 terminally ill possums. Subcutaneous lesions were suppurative in nature, often discharging through sinuses to the exterior. Histologically, the smallest lesions comprised focal aggregations of macrophages with angulated cytoplasmic boundaries occasionally containing acid-fast organisms. Larger lesions were pyogranulomatous, with extensive necrosis, caseation and large numbers of intra- and extra-cellular acid-fast organisms. Few multinucleate giant cells were seen and fibroplasia was rare. Mineralisation was recorded in tuberculous lymph nodes from only two possums. Histological evidence of haematogenous and lymphatic spread was seen in some cases.

Journal Article↗
PubMed1995

Naturally occurring tuberculosis caused by Mycobacterium bovis in brushtail possums (Trichosurus vulpecula): III. Routes of infection and excretion.

Mycobacterium bovis was cultured from nine of 25 (36%) tracheal washings but not from any of 38 urine and 38 faecal samples from tuberculous possums cross-sectionally sampled from the wild. One of three tracheal washings, one of three urine samples and one of three faecal samples from terminally ill possums were culture-positive. The respiratory route is implicated as the major route of excretion of Mycobacterium bovis from naturally infected possums in horizontal transmission. Tuberculosis was observed in two young possums and was evidence of probable pseudo-vertical transmission via the respiratory route or ingestion of milk. Discharging fistulae were present in 22 of 71 (31%) cross-sectionally sampled tuberculous possums and were associated with relatively advanced disease. Although the frequent involvement of superficial lymphocentres in early stage disease could not be explained satisfactorily, the respiratory route was implicated as the main route of infection from indirect evidence.

Journal Article↗
PubMed1995

Primary intraosseous fibrosarcoma in a cat.

A case of primary intraosseous fibrosarcoma of the left femur in a cat was diagnosed at necropsy following 9 months of managing a fracture of the same bone. Case features were those of probable pathological fracture, fracture repair and ultimate lysis of all but a fragment of the distal femoral epiphysis. Histology revealed closely packed whorls of fibroblasts typical of fibrosarcoma. This neoplasm is rare in the cat.

Journal Article↗
PubMed1995

Broncho-oesophageal fistula in two dogs.

Two clinical cases of broncho-oesophageal fistula in the dog are presented. While both cases illustrate the value of oesophagoscopy as a diagnostic tool, one case depicts the complications which may be associated with positive contrast oesophagography. These two cases support previous observations that broncho-oesophageal fistulae are frequently of foreign body aetiology and usually extend from the caudal oesophagus, via the pleural space, to the caudal or middle right lung lobes.

Journal Article↗
PubMed1994

Comparison of a complement fixation test, a gel diffusion test and two absorbed and unabsorbed ELISAs for the diagnosis of paratuberculosis in sheep.

A complement fixation test for paratuberculosis, a gel diffusion test and two enzyme-linked immunosorbent assays (ELISA) were evaluated using sera from Mycobacterium paratuberculosis infected and non-infected sheep. Gross pathology and histopathology were used as parameters of infection. The two ELISAs, one of which is commercially available for testing cattle, were used before and after sera had been absorbed with a soluble sonicate of Mycobacterium phlei. Differences between the various tests and between ELISAs before and after absorption were non-significant (P > 0.05) in non-infected sheep or in animals with gross or histopathological lesions. The specificity of all the tests was at least 97%. Sensitivity in histopathologically positive sheep was at least 98%. Sheep from infected flocks but without histopathological lesions showed serological results which were poorly correlated between the various tests.

Animals↗
PubMed1994

Lipopigments in the brushtail possum, Trichosurus vulpecula.

Two lipopigments have been found in the hepatic and lymphoid tissues of the brushtail possum, Trichosurus vulpecula. One pigment was present in hepatocytes of five out of 15 (33%) possums from a site in the Wairarapa region in the North Island of New Zealand, but was absent from the livers of 34 possums from a site in the Manawatu. The pigment is possibly of dietary origin. An extra-hepatic lipopigment was found within macrophages in the lymph nodes of three out of 12 (25%) possums from the Wairarapa site and of five out of 14 (36%) possums from the Manawatu site. It was also found in periportal macrophages in the livers of two of the possums with hepatocellular pigmentation from the Wairarapa site. This latter pigment is ceroid, and probably reflects the degeneration of lipid.

Journal Article↗
PubMed1994

Prevalence and spatial distribution of bovine tuberculosis in brushtail possums on a forest-scrub margin.

Tuberculosis caused by Mycobacterium bovis was diagnosed in 36 of 68 (53%) brushtail possums (Trichosurus vulpecula) trapped in August 1992 from a population of exceptionally low density (trap catch <3%) on a forest-scrub margin in Westland, New Zealand. The prevalence of tuberculosis in possums, based solely on gross lesions, was at least twice that previously recorded in New Zealand, and was about seven times that recorded from the same population in 1980. More male (66%) than female (33%) possums had grossly visible tuberculous lesions. The distribution of infection appeared continuous along the forest-scrub margin. Both stoats (Mustela erminea) and one of six hares (Lepus europaeus occidentalis) trapped were also infected with M. bovis.

Journal Article↗