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Biomedical subjects

M A Gemmell

Publications and source records attributed to M A Gemmell.

At least 19 recordsLinked to original sources

Echinococcus granulosus larvae in the livers of sheep in Tunisia: the effects of host age.

A baseline survey of hepatic hydatid disease in sheep in Tunisia was undertaken. Prevalence and intensity (i.e. the number of cysts/liver) were both found to increase with age. The age-specific trends in these two parameters indicate that Echinococcus granulosus is in an endemic equilibrium steady-state in Tunisia and therefore amenable to control. The distribution of parasites within the livers of the hosts followed a negative binomial distribution. The negative binomial constant, k, increased with age, indicating that there was a lower propensity for aggregation of parasites in the hosts as the sheep became older.

Age Factors

Control of Echinococcus granulosus in Cyprus and comparison with other island models.

A control programme directed against Echinococcus granulosus was introduced into the Republic of Cyprus in 1971. In 1974, this was restricted to the areas controlled by the government of the island. The force used in the 'attack' phase included a major dog control programme. This and other measures led to the rapid 'disappearance' of the parasite and control was terminated in 1985. Subsequent studies during 1993-1996 revealed that the parasite was present in 82 (20%) villages in either dogs or food animals or both and control was re-introduced in the 'consolidation' phase with emphasis on the surveillance of E. granulosus in intermediate hosts, animal movement control and treatment of dogs in 'infected' villages. During these surveys, a major difficulty was found to be in determining whether transmission was autocthonus or introduced by animals from the areas not controlled by the government. Evidence was found to suggest the former was the most likely for the infected animals which had been born and reared far from the dividing line in the government-controlled area. A major contribution of this and other island programmes, such as those in Iceland, New Zealand, Tasmania (Australia) and the Falkland Islands, to an understanding of control planning has been the demonstration that it cannot readily be determined when eradication has been achieved and that once the costly 'attack' phase has been converted into the much more cost-effective 'consolidation' phase this must be maintained indefinitely in that phase if there is cross-border transmission as is likely to be the case in all Continental control programmes.

Animals

Risk factors associated with human cystic echinococcosis in Florida, Uruguay: results of a mass screening study using ultrasound and serology.

Sonographic evidence of asymptomatic Echinococcus granulosus lesions in the liver was found in 156 of 9,515 persons in the Department of Florida, Uruguay. The sensitivity of ELISA and latex agglutination serology compared with ultrasound was 47.6% and 28.1%, respectively, and specificity was > 85%. There was a significant positive association between positive sonography and a personal history of previous but treated Echinococcus infection while those that were seropositive but ultrasound-negative were significantly more likely to have a personal history of infection or a history of infection in their family. Prevalence of infection increased significantly with age. There was no correlation between echinococcosis and dog ownership or home slaughter of sheep but offal disposal was important, with an increased prevalence of infection of 3.2%, 2.8%, and 3.1%, respectively, in persons feeding offal to dogs or burying or burning it compared with a prevalence of 0.8-1.5% in those using other methods of disposal. Almost half the population, when questioned, seemed to have sound knowledge about E. granulosus and described correct treatment of E. granulosus in dogs but this did not affect prevalence. There was a significant positive association between infection and the presence of a fenced fruit/vegetable garden and use of rural waters, particularly the cachimba (a small dam) and the aljibe (a cistern or tank) that collect rainwater from the ground surface and roofs, respectively.

Adolescent

Rates of reinfection with Echinococcus granulosus, Taenia hydatigena, taenia ovis and other cestodes in a rural dog population in Uruguay.

A survey was undertaken to determine both the prevalence of, and reinfection rates with Echinococcus granulosus and other cestodes in the Department of Florida, Uruguay. Baseline prevalence was determined in 303 rural dogs which then, in 4 groups, were re-examined 2, 4, 8 or 12 months later. Baseline prevalences for E. granulosus, Taenia hydatigena, Taenia ovis and Dipylidium caninum were 13.2, 13.9, 2.3 and 13.2%, respectively. The frequency distribution of E. granulosus was over-dispersed. Dogs in the population became infected with E. granulosus between 2 and 4 months after treatment (prevalences at 2, 4, 8 and 12 months were 0, 6.8, 18.6 and 27.9%, respectively). There was no indication that there was a predisposition of dogs to infection with the Odds Ratio being 1.0. Dogs were infected with T. hydatigena and D. caninum within 2 months and with T. ovis between 2 and 4 months after treatment. The implications of these different rates of reinfection in the dog population on anthelmintic control strategies against cystic echinococcosis are discussed.

Age Factors

Regulation of thymus PCNA expression is altered in radiation-sensitive wasted mice.

Mice bearing the autosomal recessive mutation 'wasted' (wst/wst) express a disease syndrome characterized by neurologic dysfunction, immunodeficiency, and increased sensitivity to the killing effects of ionizing radiation relative to normal littermates (wst/-) and to parental control mice (BCF1, BALB/c, and C57BL/6). Many of these abnormalities, evident as early as 21 days of age, have been localized to thymic tissues and T-lymphocyte populations. Comparison of two-dimensional gel electrophoresis patterns of proteins from wst/wst and control mouse thymus revealed that an acidic protein with a molecular mass of approximately 30 kDa was consistently expressed at lower levels in wasted mice than in controls. Microsequencing of this protein revealed a sequence of 19 N-terminal amino acids identical to the sequence of murine proliferating cell nuclear antigen (PCNA). Northern blot analyses of PCNA expression in thymus and spleen demonstrated lower accumulation of PCNA-specific transcripts in wasted mice compared with that in controls. Because PCNA expression is associated with cell cycle progression, the percentages of thymic and splenic cells in each stage of the cell cycle were examined; there were no differences in the cell stage distribution of lymphocytes freshly isolated from wasted mice compared with littermate or parental controls. After activation with concanavalin A, however, splenocytes from wst/wst mice showed a lower percentage of cells in S phase compared with that in controls. Southern blots with PCNA probes showed that the PCNA loci from the wasted mice and their normal littermates have the same restriction maps. While differences in polymerase chain reaction (PCR) priming were obtained, these could be attributed to strain-specific differences in mouse PCNA pseudogenes. These results suggest the presence of an alteration in the pathway leading to PCNA expression in radiation-sensitive tissues of wasted mice.

Animals

Further evidence for the long distance dispersal of taeniid eggs.

Autopsy of Soay Sheep on St. Kilda revealed the presence of cysticerci of Taenia hydatigena despite the absence of the definitive host on the island. Both the intensity of infection and the prevalence increased with age implying that the sheep did not acquire immunity to reinfection or superinfection. The sheep on average ingested approximately 2.4 eggs per annum. This is far below that expected if an infected dog had visited the island even on a single occasion. The data provide evidence that taeniid eggs are being transported against the prevailing wind by wildlife from at least the nearest inhabited land mass to St Kilda some 60 km distant.

Aging

Transmission dynamics of Echinococcus granulosus, Taenia hydatigena and Taenia ovis in sheep in Uruguay.

A base-line survey was carried out on the transmission dynamics of Echinococcus granulosus, Taenia hydatigena and Taenia ovis in sheep in the Department of Florida, Uruguay. Mean life expectancy at birth of the sheep population in this Department was estimated at 3.5 and 4.8 years for male and female sheep, respectively. Both intensity and prevalence of E. granulosus infection increased with age providing no evidence that immunity was acquired in the population. This revealed that E. granulosus was only relatively stable and in an equilibrium endemic steady state with an estimate of the basic reproduction ratio (Ro) of about 1.2. The mature larval population in sheep was over-dispersed with parameter k, from fitting a negative binomial, being 0.199 and 0.556 in 42- and 54-month-old sheep, respectively. The mean number of cysts increased by 1.05 cysts per year and the infection pressure was calculated as 0.174 infections per year, implying that each infection consisted of 693.6 eggs to produce 6.03 cysts. Neither intensity nor prevalence of infection with T. hydatigena or T. ovis increased with age. This indicated that immunity was acquired to reinfection by both parasites and they were in an equilibrium hyperenedemic steady state with an estimated Ro of 4.2-5.8. Viability and fertility of E. granulosus, and viability of T. hydatigena cysts in the older age groups were low. The effects of the different transmission levels of the parasites on potential control strategies are discussed.

Animals

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics for dogs and cats.

Guidelines have been designed to assist in the planning, operation and interpretation of studies for the assessment of the efficacy of drugs against helminth parasites of dogs and cats. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on the selection of animals, housing, feeding, dose-titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities involved in the evaluation of anthelmintics to employ comparable and standard procedures and will have the added benefit of minimising the numbers of animals needed for such tests.

Animal Husbandry

Detection of retinoblastoma gene deletions in spontaneous and radiation-induced mouse lung adenocarcinomas by polymerase chain reaction.

A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma gene using histological sections from radiation-induced and spontaneous tumors as the DNA source. Six mouse Rb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mouse Rb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (5.69 Gy 60Co gamma rays or 0.6 Gy JANUS neutrons, which have been found to have approximately equal radiobiological effectiveness) were analyzed for mouse Rb deletions. Tumors in 6 neutron-irradiated mice had no mouse Rb deletions. However, 1 of 6 tumors from gamma-irradiated mice (17%) and 6 of 18 spontaneous tumors from unirradiated mice (33%) showed a deletion in one or both mouse Rb alleles. All deletions detected were in the 5' region of the mouse Rb gene.

Adenocarcinoma

Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

A series of deletions around the albino locus on mouse chromosome 7 is believed to include one or more regulatory genes that control the activities of a cluster of liver enzymes. To further characterize the functions of this region of the mouse genome, we have used quantitative two-dimensional electrophoresis to analyze the effects of two of these deletions, c3H and c14CoS, on the expression of liver proteins. More than 400 distinct protein gene products were quantitated in livers from fetal and newborn wild-type homozygous (cch/cch), heterozygous (cch/c3H or cch/c14CoS), and deletion homozygous (c3H/c3H or c14CoS/c14CoS) mice. Livers of fetal and newborn c3H heterozygotes and homozygous wild-type littermates produced qualitatively identical protein patterns after two-dimensional electrophoresis. In livers of c3H homozygous fetuses, however, abnormal amounts (either increased or decreased relative to homozygous wild-type and heterozygous littermates) of 29 proteins were found. Twenty-eight of these 29 protein anomalies were also found in livers of newborn c3H homozygotes. Livers of fetal and newborn mice homozygous for the c14CoS deletion, which overlaps the c3H deletion and produces a similar phenotype, expressed normal amounts of these proteins. One of the 29 proteins (MSN807) has an amino-terminal sequence similar to a 23-kDa translationally controlled protein abundant in mouse erythroleukemia and sarcoma-180 cells. These results suggest that normal chromosome 7 contains genes, located within the region of the c3H but not the c14CoS deletion, that regulate the abundance of specific proteins in the liver. These proteins cannot be related to the phenotypic alterations shared by the c3H and c14CoS deletions.

Albinism

Efficacy of a drug combination of praziquantel, pyrantel embonate, and febantel against helminth infections in dogs.

Tablets containing praziquantel, pyrantel embonate, and febantel were tested for efficacy against helminths in dogs. A single treatment with this drug combination gave 100% reductions in Toxocara canis and Taenia hydatigena in experimentally induced infections in dogs. In dogs with naturally acquired infections, treatment gave > 97 to 98% reductions in fecal egg counts attributable to Toxascaris leonina, T canis, and Uncinaria stenocephala. Efficacy against Trichuris vulpis was > 92%.

Animals

A comparative study of the effects of clofibrate, ciprofibrate, WY-14,643, and di-(2-ethylhexyl)-phthalate on liver protein expression in mice.

Chemical, physical, or mechanical insults to a cellular system cause changes in the rates of protein synthesis or degradation. To define patterns of quantitative protein changes and identify the biochemical basis of those changes, we are studying fluctuations in mouse liver protein abundance in response to factors such as stages of maturation, changes in diet, and exposure to chemicals. Two-dimensional gel electrophoresis (2DE) together with computer-assisted data analysis is used to collect quantitative data from groups of 2DE patterns. Our analysis of liver protein expression in mice treated with four different chemicals known to cause peroxisome proliferation serves as an example of the changes in protein expression that can be monitored by using this approach. The database we are building indicates that changes specific to a particular treatment as well as generalized effects can be identified, providing the opportunity to identify patterns of protein expression that are indicators of biological response to different types of cellular insults.

Animals

Australasian contributions to an understanding of the epidemiology and control of hydatid disease caused by Echinococcus granulosus--past, present and future.

For several years after Echinococcus granulosus was introduced into Australasia from Europe, its life cycle was unknown. Before the end of the 19th century, however, Cystic Hydatid Disease (CHD) was recognized in humans as an important cause of death, although its magnitude was not quantified. During the first 50 years of the 20th century, the urban component declined, but CHD remained a serious source of ill-health. During the second half of the 20th century major research contributions have included: (i) differentiation of pastoral from wildlife Echinococcus and (ii) breaking the 'epidemiological code' of the family Taeniidae, thereby defining the conditions under which transmission occurs. Based on this research and concurrent surveys, it is concluded that the present geographical distribution of E. granulosus in domestic animals and CHD in the rural population is determined by climate; being uncommon where hot dry seasons continue beyond a few months. The parasite's range may be extended in its wildlife cycle through a highly susceptible definitive host--the dingo. The ease with which blowflies transfer taeniid eggs from dog faeces to animal and human foodstuffs implies that in Australasia, CHD can sometimes be regarded as foodborne. A perceived decline in autochthonus cases in the rural community during the second half of the 20th century may be accounted for by increased standards of living generated by economic advancement. Where a decline has not occurred or incidence is unusually high, CHD may be acting as an indicator of social disadvantage. Field trials and control programmes demonstrated that pastoral echinococcosis readily responded to intervention. Indeed, in both New Zealand and Tasmania, using different administrative structures and methods of funding, E. granulosus was driven from endemic towards extinction status. The really convincing result was the rapid decline in CHD in all age groups. The problem still to be solved is to identify methods for eliminating foci where high levels of CHD still exist but, continent- or even state-wide intervention may not be considered to be cost-effective using current tools. Here, mathematical modelling and cost-benefit analysis can be regarded as powerful methods to assist the decision-making process.

Animals

The analysis of recessive lethal mutations in mice by using two-dimensional gel electrophoresis of liver proteins.

We have used two-dimensional gel electrophoresis (2DE) coupled with computer-assisted data analysis to analyze liver-protein expression in mice known to be heterozygous carriers of recessive lethal mutations induced in In(1)1Rk or In(7)13Rk inversion stocks by exposure to either triethylene melamine or ionizing radiation. Carriers of 8 different mutations and corresponding littermate controls (average of 17 individuals in each group) were screened for liver-protein differences. Both qualitative and quantitative protein differences were detected that correlated with unique pedigrees among the mouse stocks analyzed. Such strain-specific differences demonstrated that quantitative differences (either increases or decreases) in protein abundance of greater than 25% can be readily detected by using this 2DE system. Thus the 50% reduction in expression of a protein expected in the event of a structural gene deletion is well within the level of detection. No significant quantitative decreases in protein expression that correlated with the recessive lethal mutations were detected, however.

Animals