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J D Foster

Publications and source records attributed to J D Foster.

At least 19 recordsLinked to original sources
PubMed2006

Regulation of the dopamine transporter by phosphorylation.

The dopamine transporter (DAT) is a neuronal phosphoprotein and target for psychoactive drugs that plays a critical role in terminating dopaminergic transmission by reuptake of dopamine from the synaptic space. Control of DAT activity and plasma membrane expression are therefore central to drug actions and the spatial and temporal regulation of synaptic dopamine levels. DATs rapidly traffic between the plasma membrane and endosomal compartments in both constitutive and protein kinase C-dependent manners. Kinase activators, phosphatase inhibitors, and transported substrates modulate DAT phosphorylation and activity, but the underlying mechanisms and role of phosphorylation in these processes are poorly understood. Complex adaptive changes in DAT function potentially related to these processes are also induced by psychostimulant and therapeutic transport blockers such as cocaine and methylphenidate. This chapter provides an overview of the current state of knowledge regarding DAT phosphorylation and its relationship to transporter activity and trafficking. A better understanding of how dopaminergic neurons regulate DAT function and the role of phosphorylation may lead to the identification of novel therapeutic targets for the treatment and prevention of dopaminergic disorders.

Amphetamine↗
PubMed2005

Modelling the spread of scrapie in a sheep flock: evidence for increased transmission during lambing seasons.

Presence of scrapie infectivity in the placenta suggests the possibility of increased transmission of scrapie during the lambing season. This hypothesis was explored here using a mathematical model of scrapie transmission dynamics which has previously been successfully used to study several scrapie outbreaks in Scottish sheep flocks. It was applied here to the Langlade experimental sheep flock (INRA Toulouse, France), in which a natural scrapie epidemic started in 1993. Extensive data were available, including pedigree, scrapie histopathological diagnoses and PrP genotypes. Detailed simulations of the scrapie outbreak reveal that the observed patterns of seasonality in incidence can not be accounted for by seasonality in demography alone and provide strong support for the hypothesis of increased transmission during lambing. Observations from several other scrapie outbreaks also showing seasonal incidence patterns support these conclusions.

Age Factors↗
PubMed2004

Maternal transmission studies of BSE in sheep.

If BSE (bovine spongiform encephalopathy) infected the UK sheep population concurrently with cattle, it would only now be maintained by transmission between sheep by routes which could include from mother to lamb either in utero or via perinatal close contact. In this study of experimental BSE, Cheviot ewes challenged orally with BSE cattle brain produced lambs of various PrP genotypes over the next 7 years. Of 72 surviving to >30 months of age, 29 are of the most susceptible PrP genotype (AQ/AQ) and born to mothers that were challenged with BSE. None of the progeny have shown any signs of disease. The results suggest that in these sheep, BSE could only transmit by the maternal route at a frequency of less than one in four (95 % confidence limit) from clinically affected ewes, a rate which if replicated in other breeds may not be sufficient to maintain BSE within the sheep population.

Animals↗
PubMed2002

Comparative epidemiology of scrapie outbreaks in individual sheep flocks.

Data recording the course of scrapie outbreaks in 4 sheep flocks (2 in Cheviot sheep and 2 in Suffolks) are compared. For each outbreak the data on scrapie incidence and sheep demography and pedigrees cover periods of years or decades. A key finding is that the incidence of clinical cases peaks in sheep 2-3 years old, despite very different forces-of-infection. This is consistent with age-specific susceptibility of sheep to scrapie, as has been reported for cattle to bovine spongiform encephalopathy and for humans to variant Creutzfeldt-Jakob disease. Scrapie incidence was higher in ewes than rams and at certain times of years, though these effects were not consistent between flocks. There was no evidence for high levels of vertical transmission.

Age Factors↗
PubMed2001

Discriminant responses of the catalytic unit and glucose 6-phosphate transporter components of the hepatic glucose-6-phosphatase system in Ehrlich ascites-tumor-bearing mice.

The effect of Ehrlich ascites tumor cells, in vivo, on the hepatic glucose-6-phosphatase (G6Pase) system was examined. The V(max) for glucose 6-phosphate hydrolysis by G6Pase was reduced by 40% and a greater than 15-fold decrease in mRNA encoding the catalytic unit of the G6Pase system was observed 8 days after injection with tumor cells. Blood glucose concentration was decreased from 169 +/- 17 to 105 +/- 9 mg/dl in tumor-bearing mice. There was no change in the G6P transporter (G6PT) mRNA level. However, there was a significant decrease in G6P accumulation into hepatic microsomal vesicles derived from tumor-bearing mice. Decreased G6P accumulation was also associated with a decrease in G6Pase hydrolytic activity in the presence of vanadate, a potent catalytic-unit inhibitor. In addition, G6P accumulation was nearly abolished in microsomes treated with N-bromoacetylethanolamine phosphate, an irreversible inhibitor of the G6PT. These results demonstrate that the catalytic unit and G6PT components of the G6Pase system can be discriminantly regulated, and that microsomal glucose 6-phosphate uptake is dependent on catalytic unit activity as well as G6PT action.

Animals↗
PubMed2001

Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats.

This paper compares the dinical signs, histopathology, detection of PrPSc protein and PrP genetics of the transmission of BSE to sheep and goats, with the effects of the transmission of natural scrapie from a brain homogenate from a single sheep. After intracerebral and oral inoculations there were similarities in the clinical signs due to the two sources of infection, but there were differences in pathology at the end stage of disease and in the genotypes of the sheep which succumbed to the challenges. The incubation period of BSE was associated with the sheep PrP codon 171 genotype, but the natural scrapie source, despite inducing disease only in known susceptible genotypes, showed no clear association with PrP genotype.

Animals↗
PubMed2001

Population dynamics of a scrapie outbreak.

A detailed analysis of a scrapie outbreak in a flock of Cheviot sheep is described. A total of 33 cases of 1473 sheep born to the flock were reported between 1985 and 1994. The epidemiology of scrapie can only be understood with reference to sheep demography, the population genetics of susceptibility to scrapie, pathogenesis during a long incubation period, and the rate of transmission (by both horizontal and vertical routes), all of which interact in complex ways. In recent work a mathematical model incorporating these elements was developed and successfully reproduced key features of an earlier outbreak of scrapie in this flock. Here an application of the model to the second outbreak is described. The model accurately reproduces observed allele frequencies and total numbers of susceptible animals remaining at the end of the outbreak. A major difference between the two outbreaks is the very much lower force of infection in the second outbreak. This provided additional information which suggested two ways in which our existing assumptions be refined; firstly, older animals have reduced susceptibility to scrapie and secondly, homozygous and heterozygous susceptibles have different incubation periods.

Animals↗
PubMed2001

A centuries-long epidemic of scrapie in British sheep?

The apparent persistence of scrapie in British sheep for more than 250 years is difficult to explain. Susceptibility to scrapie is associated with particular alleles at a single locus, the PrP gene. As the only known effect of these alleles is to confer susceptibility to a fatal disease, natural selection is expected to reduce their frequency, as has been observed in practice during scrapie outbreaks in single sheep flocks. Susceptibility alleles, and hence scrapie itself, are therefore expected to become rare, yet the disease remains widespread. We suggest that the paradox of scrapie's persistence can be explained by the exceptionally long time-scales inherent in the epidemiology of the disease. It is proposed that scrapie should be regarded as epidemic in British sheep but, unlike more familiar epidemics, which have time-scales of months or years, the scrapie epidemic has a time-scale of centuries. This interpretation implies that scrapie should eventually disappear from the sheep population.

Animals↗
PubMed2001

Distribution of the prion protein in sheep terminally affected with BSE following experimental oral transmission.

This study has examined the distribution of PrP(Sc) in sheep by immunocytochemistry of tissues recovered from terminally affected animals following their experimental infection by the oral route with BSE. Despite a wide range of incubation period lengths, affected sheep showed a similar distribution of high levels of PrP(Sc) throughout the central nervous system. PrP(Sc) was also found in the lymphoid system, including parts of the digestive tract, and some components of the peripheral nervous system. These abundant PrP(Sc) deposits in sheep in regions outside the central nervous system are in direct contrast with cattle infected with BSE, which show barely detectable levels of PrP(Sc) in peripheral tissues. A number of genetically susceptible, challenged animals appear to have survived.

Animals↗
PubMed2000

Transmission of BSE by blood transfusion in sheep.

We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) In human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission--this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK.

Animals↗
PubMed2000

N-Bromoacetylethanolamine phosphate as a probe for the identification of a liver microsomal glucose-6-phosphate transporter peptide in rats and Ehrlich ascites tumor-bearing mice.

Hepatic microsomal glucose-6-phosphatase is a multicomponent system composed of substrate/product translocases and a catalytic subunit. Previously we (Foster et al. (1996) Biochim. Biophys. Acta 12, 244-254) demonstrated that N-bromoacetylethanolamine phosphate (BAEP) is a time-dependent, irreversible inhibitor of glucose-6-phosphate hydrolysis in intact but not disrupted microsomes. We proposed that BAEP manifests its inhibitory effect by binding with a glucose-6-phosphate translocase protein of the glucose-6-phosphatase system. Here we provide additional evidence that BAEP inhibits glucose-6-phosphate transport in microsomal vesicles and utilize [(32)P]BAEP as an affinity label in the identification of a glucose-6-phosphate transport protein. In this study, we identify 51-kDa rat and mouse liver microsomal proteins involved in glucose-6-phosphate transport into and out of microsomal vesicles by utilizing (1) an Ehrlich ascites tumor-bearing mouse model, which displays a decreased sensitivity to the time-dependent inhibitory effect of BAEP, and (2) another glucose-6-phosphate translocase inhibitor, tosyl-lysine chloromethyl ketone, in conjunction with [(32)P]BAEP as an affinity label.

Affinity Labels↗
PubMed1999

Population dynamics of scrapie in a sheep flock.

A detailed analysis of an outbreak of natural scrapie in a flock of Cheviot sheep is described. A total of 137 cases was reported over 13 years among 1307 sheep born into the flock. The epidemiology of scrapie can only be understood with reference to sheep demography, the population genetics of susceptibility to scrapie, pathogenesis during a long incubation period, and the rate of transmission (by both vertical and horizontal routes), all of which interact in complex ways. A mathematical model incorporating these features is described, parameter values and model inputs are derived from available information from the flock and from independent sources, and model outputs are compared with the field data. The model is able to reproduce key features of the outbreak, including its long duration and the ages of cases. The analysis supports earlier work suggesting that many infected sheep do not survive to show clinical signs, that most cases arise through horizontal transmission, and that there is strong selection against susceptible genotypes. However, important aspects of scrapie epidemiology remain poorly understood, including the possible role of carrier genotypes and of an environmental reservoir of infectivity, and the mechanisms maintaining alleles giving susceptibility to scrapie in the sheep population.

Alleles↗
PubMed1999

Olfactory secretion and sodium, potassium-adenosine triphosphatase: regulation by corticosteroids.

OBJECTIVES: To investigate the cellular distribution and relative intensity of the immunoreactivity associated with the expression of sodium, potassium-adenosine triphosphatase (Na, K-ATPase) in cells of the olfactory mucosa. Second, changes in the activity of this enzyme in the olfactory mucosa are correlated with changes in the circulating corticosteroid aldosterone. METHODS: Combination of immunohistochemical and biochemical techniques were employed to examine the olfactory Na, K-ATPase. RESULTS: Within the olfactory epithelium, the Na, K-ATPase immunoreactivity was greatest at the supranuclear region of sustentacular cells and/or dendrites of olfactory receptor neurons (ORNs). Cell bodies of ORNs demonstrated moderate immunoreactivity, whereas the duct cells of Bowman's gland exhibited moderate to intense immunoreactivity. Acinar cells of the Bowman's gland were the most intensely stained components of the lamina propria, exhibiting strong immunoreactivity at the basolateral plasma membrane domains of the acinar cells and less within the cytoplasm. Binding of ouabain, a specific inhibitor of Na, K-ATPase, was significantly elevated for aldosterone-injected versus sham-injected controls. CONCLUSION: These results suggest that olfactory Na, K-ATPase is regulated by the systemic corticosteroid aldosterone. The results are consistent with the hypothesis that corticosteroids regulate olfactory secretion.

Aldosterone↗
PubMed1999

Regulation of glucose production by the liver.

Glucose is an essential nutrient for the human body. It is the major energy source for many cells, which depend on the bloodstream for a steady supply. Blood glucose levels, therefore, are carefully maintained. The liver plays a central role in this process by balancing the uptake and storage of glucose via glycogenesis and the release of glucose via glycogenolysis and gluconeogenesis. The several substrate cycles in the major metabolic pathways of the liver play key roles in the regulation of glucose production. In this review, we focus on the short- and long-term regulation glucose-6-phosphatase and its substrate cycle counter-part, glucokinase. The substrate cycle enzyme glucose-6-phosphatase catalyzes the terminal step in both the gluconeogenic and glycogenolytic pathways and is opposed by the glycolytic enzyme glucokinase. In addition, we include the regulation of GLUT 2, which facilitates the final step in the transport of glucose out of the liver and into the bloodstream.

Animals↗
PubMed1999

Mineralocorticoid receptors in the mammalian olfactory mucosa.

Mineralocorticoid hormones regulate secretion and absorption in a wide variety of epithelial tissues, although specific mechanisms in the olfactory mucosa are currently unknown. Utilizing reverse transcription-polymerase chain reaction (RT-PCR) analysis, we have demonstrated the expression of mineralocorticoid (type I) receptor messenger RNA in the rodent olfactory mucosa. Amplification products of predicted size were obtained with nucleotide sequences corresponding to respective mineralocorticoid receptor (MR) kidney transcripts. Immunocytochemistry, using an antibody with known specificity for MRs, was then utilized in order to localize the cellular site(s) of MR protein expression in the olfactory mucosa. The highest levels of MR immunoreactivity were localized to the supranuclear region of sustentacular cells, as well as the acinar cells of the Bowman's glands. The respiratory regions of the nasal cavity were devoid of appreciable MR immunoreactivity. This study demonstrates both MR transcript and protein expression in the olfactory mucosa. We hypothesize that the mineralocorticoid hormones may have a role in modulation of olfactory secretion and/or sensory transduction in the peripheral olfactory system.

Animals↗
PubMed1998

Histone II-A activates the glucose-6-phosphatase system without microsomal membrane permeabilization.

Many agents have been used to release the latent portion of the activities catalyzed by the glucose-6-phosphatase (Glc-6-Pase) system. Detergents, which disrupt the microsomal membrane concomitantly with Glc-6-Pase activation, have been the most widely used of these agents. The treatment of microsomes with alamethicin or histone II-A has also been reported to activate the Glc-6-Pase system to the same extent as detergent treatment. While alamethicin reportedly permeabilizes the microsomal membrane (R. Fulceri et al., 1995, Biochem. J. 307, 391-397), conflicting ideas as to histone II-A's mechanism of activation have been described (J. St.-Denis et al., 1995, Biochem. J. 310, 221-224 and J. Blair and A. Burchell, 1988, Biochim. Biophys. Acta 964, 161-167). We further investigated whether activation of the Glc-6-Pase system by histone II-A is due to permeabilization of the microsomal membrane. We treated rat liver microsomes with Triton X-100, alamethicin, or histone II-A and found them to be equally effective in maximally activating the Glc-6-Pase system. We also examined the modifying effects of alamethicin and histone II-A on the sensitivity of Glc-6-Pase activities to inhibition by N-bromoacetylethanolamine phosphate (BAEP) and 3-mercaptopicolinate (3-MP), both thiol-directed reagents. Alamethicin, but not histone II-A, abolished the inhibitory effects of BAEP and 3-MP on activities of the Glc-6-Pase system. Our studies support previous reports of Glc-6-Pase activation by alamethicin via permeabilization of microsomal membranes and histone II-A activation without microsomal membrane permeabilization.

Alamethicin↗
PubMed1998

Tungstate: a potent inhibitor of multifunctional glucose-6-phosphatase.

The insulin-like action of tungstate in diabetic rats (A. Barberà et al., 1994, J. Biol. Chem. 269, 20047-20053) prompted us to examine the effects of tungstate on the glucose-6-phosphatase system. Our results indicate that tungstate is a potent inhibitor of glucose-6-phosphatase, with a Ki in the 10-25 microM range determined with native microsomes and in the 1-7 microM range determined with detergent-treated microsomes. With both preparations, simple linear competitive inhibition was observed versus glucose 6-phosphate (glucose-6-P) as substrate with the glucose-6-P phosphohydrolase activity of the enzyme. Tungstate was a simple linear competitive inhibitor versus carbamyl phosphate (carbamyl-P) and a linear noncompetitive inhibitor versus glucose with the carbamyl-P:glucose phosphotransferase activity of the glucose-6-phosphatase system. These findings, in addition to the observation that tungstate protected the enzyme against thermal inactivation, indicate that tungstate binds with high affinity and competes at the active site of the enzyme where the substrates glucose-6-P and carbamyl-P bind prior to catalysis. Our results suggest that potent inhibition of glucose-6-P hydrolysis by tungstate is likely responsible, at least in part, for the normalization of glycemia and the rebound in hepatic glucose-6-P levels observed in earlier studies in which tungstate exhibited insulin-like action in diabetic rats.

Animals↗