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Biomedical subjects

J D Foster

Publications and source records attributed to J D Foster.

At least 73 records · Page 4Linked to original sources

Bovine brain acetylcholinesterase primary sequence involved in intersubunit disulfide linkages.

Three distinct classes of membrane-bound acetylcholinesterases (AChEs) have been identified. A12 AChE is composed of 12 catalytic subunits that are linked to noncatalytic collagen-like subunits through intersubunit disulfide bonds. G2 AChE is localized in membranes by a glycoinositol phospholipid covalently linked to the C-terminal amino acid. Brain G4 AChE involves two catalytic subunits linked by a direct intersubunit disulfide bond while the other two are disulfide-linked to a membrane-binding 20-kDa noncatalytic subunit. Molecular cloning studies have so far failed to find evidence of more than one AChE gene in any organism although alternative splicing of torpedo AChE mRNA results in different C-terminal sequences for the A12 and G2 AChE forms. Support for a single bovine AChE gene is provided in this report by amino acid sequencing of the N-terminal domains from the G2 erythrocyte, G4 fetal serum, and G4 brain AChE. Comparison of the 38-amino acid sequences reveals virtually complete identity among the three AChE forms. Additional extensive identity between the fetal serum and brain AChEs was demonstrated by sequencing several brain AChE peptides isolated by high performance liquid chromatography after trypsin digestion of nitrocellulose blots of brain AChE catalytic subunits. Cysteines involved in intersubunit disulfide linkages in brain AChE were reduced selectively with dithiothreitol in the absence of denaturants and radioalkylated with iodoacetamide. The observed sequence of the major radiolabeled tryptic peptide was C*SDL, where C* was the radioalkylated cysteine residue. This sequence is precisely the same as that observed at the C terminus of fetal bovine serum AChE and shows close homology to the C-terminal sequence of torpedo A12 AChE. We conclude that the mammalian brain G4 AChEs utilize the same exon splicing pattern as the A12 AChEs and that factors other than the primary sequence of the AChE catalytic subunits dictate assembly with either the collagen-like or the 20-kDa noncatalytic subunits.

Acetylcholinesterase↗

Identification of sugar residues in secretory glycoconjugates of olfactory mucosae using lectin histochemistry.

Lectin histochemistry at the light microscope level was used to determine the distribution of sugar residues in secretory cells of the olfactory mucosae of salamander, hamster, and mouse. Differences in sugar composition and distribution of glycoconjugates found in sustentacular cells and acinar cells of Bowman's glands of these three animals were characterized. Oligosaccharides in secretory products of sustentacular cells in salamander olfactory mucosa contained sialic acid, galactose (Gal), N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc), fucose, and mannose residues. Glycoconjugates of these cells lacked terminal galactosyl-beta-(1,3)N-acetylgalactose (Gal beta 1,3GalNAc) residues. The sequences Gal beta 1,3GalNAc, N-acetyllactosamine (Gal beta 1,4GlcNAc), and GalNAc were penultimate to sialic acid residues. Sustentacular cells of mouse and hamster did not appear to contain O-linked oligosaccharides but stained for mannose-containing N-linked oligosaccharides. Glycoconjugates of acinar and duct cells of Bowman's glands in the salamander, hamster, and mouse contained variable amounts of beta(1,4)GlcNAc residues, and terminal N-acetyllactosamine, Gal beta 1,3GalNAc, and GalNAc residues. In the salamander, glycoconjugates of acinar cells possessed terminal GlcNAc residues but were not sialylated, while those of hamster and mouse generally stained for sialic acid but did not possess terminal GlcNAc residues. Secretory products of a subpopulation of rodent acinar cells also contained penultimate Gal beta 1,3GalNAc residues. Staining for sialic acid, Gal, GalNAc, and GlcNAc in glycoconjugates of rodents was often limited to a sub-population of Bowman's glands. This was especially noticeable in the mouse.

Ambystoma↗

Metabolic intermediates as potential regulators of glucose-6-phosphatase.

Twenty-five metabolites of glucose, gluconeogenic substrates, and related compounds were examined as potential inhibitors of glucose-6-phosphatase (EC 3.1.3.9) catalytic unit and substrate transport function, using disrupted and intact rat liver microsomes. Inhibitions (competitive) were noted with six. Calculated per cent inhibitions with presumed near-physiologic concentrations of inhibitor and substrate were small. However, when hepatic fructose-1-P concentration is elevated in response to a fructose load, inhibition of glucose-6-phosphatase by fructose-1-P may play a regulatory role, along with fructose-1-P-associated deinhibition of glucokinase, by directing glucose-6-P away from glucose formation and towards glycogen synthesis and glycolysis.

Animals↗

Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene.

The incubation period of scrapie in sheep is controlled by the Sip gene which has two alleles (sA and pA). Following experimental challenge with SSBP/1 scrapie, a short incubation period is conferred by the partially dominant sA allele. Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene are associated with the Sip alleles. By sequencing the protein coding region of the PrP gene in Cheviot sheep selected for differing Sip genotypes, we have found four PrP protein variants which differ at three positions: amino acid 112 (Ala/Val), amino acid 130 (Arg/His) and amino acid 147 (Arg/Gln). The Val 112 variant can be distinguished at the DNA level by an RspXI restriction site which is not present in the Ala 112 form. Val 112 appears to be linked to a short incubation period of experimentally induced scrapie in the Cheviot sheep and therefore with the Sip sA allele. These results provide new evidence that the PrP protein may be a product of the Sip locus.

Alleles↗

Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and their association with susceptibility to natural scrapie in British sheep.

We have investigated the correlation between restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and the incidence of natural scrapie in British sheep during the period from July 1988 to November 1990. Sixty percent of the scrapie-positive animals studied were homozygous for a 6.8 kb EcoRI fragment (e1) and a further 26% carried e1 as heterozygotes. This fragment is linked to susceptibility to experimental scrapie in a closed flock of Cheviot sheep. Twelve percent of cases were found to be homozygous for a 4.4 kb EcoRI fragment (e3) which in the Cheviot flock had been linked to relative resistance to scrapie. A third EcoRI fragment of 5.2 kb (e2) has also been found but is relatively rare and has not yet been associated with scrapie susceptibility. Four sets of flocks affected by natural outbreaks of scrapie divided into two groups. In three of these flocks, all scrapie cases carried e1 with high frequencies of e1e1 homozygotes. In the fourth, there were no e1e1 scrapie cases; all scrapie sheep carried e3 in approximately equal numbers of heterozygotes and homozygotes.

Animals↗

New Jersey high school students' knowledge, attitudes, and behavior regarding AIDS.

In 1988 a questionnaire was administered to 1,793 urban and suburban New Jersey high school students to survey their knowledge, attitudes, and behavior related to the acquisition of acquired immunodeficiency syndrome (AIDS). Knowledge about the disease was high, but exaggeration of risk from social contacts was common. Although fear was associated with misperceptions, it was not always dispelled by knowledge. Nearly half (49%) of all participants reported having used condoms, indicating that condom use is somewhat familiar and acceptable to them. Over 80% thought that condoms offer some protection against AIDS. However, knowledge did not always result in recognition or practice of risk-reduction behaviors. Student suggestions for slowing the spread of AIDS stressed personal responsibility and education. Follow-up assemblies that used survey results to address gaps in knowledge appeared necessary to counter misperceptions that might have arisen from the survey.

Acquired Immunodeficiency Syndrome↗

Two alleles of a neural protein gene linked to scrapie in sheep.

Sheep are the natural hosts of the pathogens that cause scrapie, an infectious degenerative disease of the central nervous system. Scrapie-associated fibrils [and their major protein, prion protein (PrP)] accumulate in the brains of all species affected by scrapie and related diseases. PrP is encoded by a single gene that is linked to (and may be) the major gene controlling the incubation period of the various strains of scrapie pathogens. To investigate the role of PrP in natural scrapie, we have determined its gene structure and expression in the natural host. We have isolated two sheep genomic DNA clones that encode proteins of 256 amino acids with high homology to the PrPs of other species. Sheep PrPs have an arginine/glutamine polymorphism at position 171 that may be related to the alleles of the scrapie incubation-control gene in this species.

Alleles↗

The use of monosodium glutamate in identifying neuronal populations in mice infected with scrapie.

The excitatory amino-acid, monosodium glutamate, which causes degeneration in the retinal ganglion cells in neonatal mice, was used to investigate the transport of scrapie within optic nerve axons. In treated mice, there was prolongation of the incubation period following intraocular infection with the ME7 strain of scrapie, and a decrease in the severity of retinopathy after intracerebral infection with the 79A strain. These data confirm that scrapie infection spreads along neural pathways, and demonstrate the potential use of selective neurotoxins to study pathogenesis.

Animals↗

Age at death from natural scrapie in a flock of Suffolk sheep.

This study deals with natural scrapie in a flock of Suffolk sheep being bred to maximise the incidence of the disease and shows that with succeeding generations the incubation period of the disease became progressively shorter until the flock died out. The most likely explanation for this phenomenon is considered to be an increase in the load of infection.

Age Factors↗

Linkage of the gene for the scrapie-associated fibril protein (PrP) to the Sip gene in Cheviot sheep.

The gene Sip with two alleles, sA and pA, is the major gene determining the incubation period of scrapie in its natural host, sheep. Two lines of Cheviot sheep have been bred which differ in their response to experimental infection with SSBP/1 scrapie. The negative line have a decreased incidence of disease caused by SSBP/1 and are SippApA. The positive line have an increased incidence of disease and the majority are either SipsAsA or SipsApA; it is not possible to distinguish between the two genotypes on the basis of scrapie incubation time because the sA allele is fully dominant with SSBP/1 scrapie. There are also rare SippApA segregants in the positive line. The major protein (PrP) of scrapie-associated fibrils is encoded by a cellular gene and a cDNA copy of the hamster PrP mRNA has been used to analyse the restriction fragment length polymorphism of the two lines of Cheviot sheep. Two polymorphisms of the sheep PrP gene were found, by using HindIII and EcoRI, which appear to act as markers for the alleles of Sip. Using these polymorphisms it is now possible to assign a Sip genotype to the sheep in the Cheviot flock. Preliminary results from Anglo-Nubian goats and a cow are also reported.

Alleles↗

The unusual properties of CH1641, a sheep-passaged isolate of scrapie.

An isolate of scrapie designated CH1641 was identified from a natural case of scrapie in a Cheviot sheep by passage in sheep and goats. It has not been possible to transmit scrapie to mice from this source. The Sip gene which controls the incubation periods of experimental scrapie in Cheviot sheep has two alleles; sA which shortens and pA which lengthens the incubation periods of most strains of scrapie after the first experimental injection in sheep (the A group of strains). The CH1641 isolate differs from them in that the alleles of Sip act in the opposite way, with incubation being shorter in the pA homozygotes. There is some evidence that one or more genes, in addition to Sip, may be implicated in the control of scrapie incubation in sheep and the possibility of a carrier infection with CH1641 is also discussed.

Alleles↗

In situ/invasive cervical cancer ratios: impact of cancer education and screening.

A study of cancer incidence rates in Newark, NJ showed an increase in invasive cervical cancer among black women between 1970 and 1976. The incidence was substantially higher than that found in the Third National Cancer Survey and the Surveillance Epidemiology End Results Program. The ratio of in situ/invasive cervical cancer incidence among black women was 1:1, far below the national ratio of about 3:1. It seemed that the high-risk population in Newark might not be having regular Papanicolaou smears. From 1976 through 1981, intensive educational and cervical cancer screening programs were carried out in the city of Newark. A review was made of cervical cancer cases (1976-1981) reported to the tumor registries or recorded on discharge diagnoses in hospitals where Newark residents are known to have sought care. The findings showed that the ratio of in situ to invasive cervical cancer had increased dramatically: the overwhelming majority of cancers were found to be in situ carcinomas. The improvement was far more impressive among black women than among white women. Since the intervention campaign had been directed primarily toward the black female population, a group at extremely high risk, this suggested that efficacy of the intervention program.

Adolescent↗

Scrapie associated fibrils in the diagnosis of scrapie in sheep.

Previous research has consistently demonstrated by electron microscopy the presence of scrapie associated fibrils in brain extracts prepared from mice and hamsters with clinical signs of experimental scrapie. In the present study similar fibrils were seen in all the brain extracts prepared from 11 Cheviot or Suffolk sheep with natural or experimental scrapie that had been diagnosed clinically and confirmed neuropathologically. They were not found in the brain extracts of nine sheep that did not have scrapie and which included four that had been injected with infected material but did not develop the disease. The presence of such fibrils can therefore be used as an additional diagnostic criterion for natural scrapie in sheep.

Animals↗

Primary retinopathy in scrapie in mice deprived of light.

Rodents infected with some strains of scrapie develop a severe retinopathy in which the photoreceptor cells are destroyed. The possibility that this results from light-induced damage as a secondary consequence of the disease was tested by maintaining scrapie-infected albino mice in total darkness. Photoreceptor loss occurred in terminal scrapie-infected mice maintained in both total darkness and in normal lighting conditions establishing that the retinopathy is a primary lesion with this strain of scrapie agent.

Animals↗

Hair analysis.

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Hair↗