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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

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

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

Transmission of taeniid tapeworm eggs via blowflies to intermediate hosts.

Experiments showed that dead blowflies containing eggs of Taenia hydatigena can transmit infection if ingested by lambs during grazing. Rabbits became infected with T. pisiformis after grazing grass exposed to blowflies that had been in contact with dog faeces containing the eggs of this parasite. When captive blowflies were exposed first to dog faeces containing proglottids of T. hydatigena and then to cooked meat, 100% of pigs fed on this meat became infected. The experiments are intended to model the transmission dynamics that result in human larval tapeworm infections. The implications of the results to the epidemiology of human hydatid diseases caused by Echinococcus granulosus and E. multilocularis as well as of T. solium cysticercosis are discussed.

Animals

Population dynamics in echinococcosis and cysticercosis: regulation of Taenia hydatigena and T. ovis in lambs through passively transferred immunity.

A comparison has been made of the interactions between passively transferred and actively acquired immunity in regulating populations of Taenia hydatigena and T. ovis. When ewes were grazed prior to parturition under a high infection pressure, immunity was transferred to their offspring for up to 8 weeks. A qualitative difference between the species was the destruction of larval T. ovis prior to their establishment ('pre-encystment immunity') and that of T. hydatigena after they had become established ('post-encystment immunity') in the challenged lambs. The major difference in terms of population regulation between the two parasites was that infection occurred with T. hydatigena but not with T. ovis in those lambs reared from birth for 16 weeks under high infection pressure. Passive, like active immunity, is a density-dependent constraint. It plays an important role in the population regulation of T. ovis, but not of T. hydatigena. This is discussed in terms of transmission in the natural environment, an hypothesis on humoral protection and the need to elucidate pathways of protection when immunization schedules are being evaluated for controlling the taeniid zoonoses.

Animals

The ovine cysticercosis as models for research into the epidemiology and control of the human and porcine cysticercosis Taenia solium: I. Epidemiological considerations.

A brief review is given of the transmission dynamics of the ovine cysticercoses Taenia hydatigena and T. ovis. The importance of the basic reproductive rate (Ro) and the parasite, host and socio-ecological factors determining the epidemiological steady states of Taeniidae are described. The transmission dynamics of these ovine cysticercoses have been used as models to assist in identifying the biological and epidemiological research needed for developing strategies for the control of porcine cysticercosis caused by T. solium.

Animals

The ovine cysticercosis as models for research into the epidemiology and control of the human and porcine cysticercosis Taenia solium: II. The application of control.

Field trials and control programmes demonstrate that ovine echinococcosis (Echinococcus granulosus) and the cysticercoses (Taenia hydatigena and T. ovis) have different stabilities and may not respond in the same way to control. The first-named, which is usually in the endemic state, is readily transformed by a dog-dosing programme to extinction status. In contrast, the cysticercoses, usually in the hyperendemic state, may only be transformed to the endemic state. The consequence of this includes an increase in the larval population by superinfection due to a loss of immunity following this change in epidemiological status. These field trials and control programmes have been used as models for porcine cysticercosis caused by T. solium. It is concluded that future research should model the life cycle of this parasite mathematically and determine the most cost-effective control strategies. The impact of these on human prevalence can then be addressed by pilot field trials.

Animals

A heritable variant of mouse liver ornithine aminotransferase (EC 2.6.1.13) induced by ethylnitrosourea.

A variant of ornithine aminotransferase (OAT, EC 2.6.1.13) has been detected in an offspring of a male mouse treated with ethylnitrosourea. The evidence presented to support the identification of the protein variant (ENU 2) as altered OAT includes (a) a corresponding 50% decrease in the abundance of a protein, located one charge unit basic to the variant, which comigrates on two-dimensional gel patterns with purified mouse liver OAT; (b) the binding of anti-rat-OAT antibody to the variant; (c) the increased abundance of the variant protein in the livers of mice fed a high protein diet (85% casein); and (d) purification of the variant through an OAT purification protocol.

Animals

Protein kinase C activities with different characteristics, including substrate specificity, from two human HL-60 leukemia cell variants.

To evaluate the role of protein kinase C in the cellular maturation processes induced by phorbol diesters, we examined the biochemical activity of protein kinase C from HL-205, a cell variant from the human promyelocytic HL-60 leukemia that is susceptible to differentiation induced by phorbol 12-myristate 13-acetate, and from HL-525, an HL-60 variant that is resistant to such an induction. The activities of protein kinase C from the two cell types differed in their requirements for the cofactors Ca2+ and lipids. These enzyme activities also differed in their abilities to phosphorylate protamine and a series of four oligopeptides. We suggest that the differences in vitro in the activities of protein kinase C between HL-205 and HL-525 cells, especially in their substrate specificity, are closely related to the different phosphorylation patterns induced in vivo by phorbol 12-myristate 13-acetate in these cells. We also suggest that these differences may be responsible for the different susceptibilities of the two cell types to maturation induced by phorbol diesters.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Heritable protein variants induced by exposure to ethylnitrosourea: heritability, subcellular location, and tissue distribution.

The heritability, subcellular location, and tissue distribution of liver protein alterations found in the two-dimensional electrophoresis patterns of 4 offspring from male mice treated with N-ethyl-N-nitrosourea (ENU) were studied. Mice homozygous for each of the 4 ENU-induced protein variants were found to be viable and fertile, although the number of homozygous offspring from crosses between heterozygous carriers of one variant (ENU 2) was less than that expected for a nondetrimental trait. Two of the proteins altered by ENU-induced mutations were associated with the crude mitochondrial fraction, another was found predominantly in the microsomal fraction, and the fourth was associated with the mitochondrial, microsomal, and cytosol fractions. All of the ENU-induced mutations affected proteins that were not liver-specific; i.e., the proteins were found in other tissues in addition to the liver.

Animals