Transmission of bovine spongiform encephalopathy to sheep, goats, and mice.
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Animals↗
Biomedical subjects
J D Foster
Publications and source records attributed to J D Foster.
Glycogenesis from glucose and ureagenesis in isolated perfused rat livers. Influence of ammonium ion, norvaline, and ethoxyzolamide.
The probable involvement of hepatic carbamyl-P in the reciprocal relationship between hepatic ureagenesis and glycogenesis from glucose was explored. Isolated perfused liver preparations from 48-h fasted rats were employed. Moderate (9.2 mM) and relatively high levels of glucose (34 mM) were perfused. Hepatic glycogenesis, glucose-6-P, carbamyl-P, and citrulline levels, hepatic urea formation, and ureagenesis based upon perfusate urea levels were measured. Experimental probes selected to modify hepatic ureagenesis and carbamyl-P production and utilization included: (a) NH4Cl, maintained at 5 mM by continuous infusion (NH4+ is a substrate for carbamyl-P synthase I and glutamate dehydrogenase); (b) norvaline, an inhibitor of ornithine transcarbamylase which catalyzes the first committed step in the urea cycle; and (c) ethoxyzolamide, an inhibitor of carbonic anhydrase which produces HCO3-, an essential substrate for carbamyl-P synthase I. NH4+ increased ureagenesis and decreased glycogenesis. The inclusion of norvaline with NH4+ decreased ureagenesis and increased glycogenesis. Ethoxyzolamide with or without NH4+ inhibited both ureagenesis and glycogenesis, and decreased the hepatic glucose-6-P level. Glycogenesis was greater at 34 mM than 9.2 mM glucose, increased in norvaline-containing preparations correlative with increased availability of carbamyl-P, and decreased when carbamyl-P formation was inhibited by ethoxyzolamide. Kinetic analysis indicated a Km, Glc of 31 mM for glucose phosphorylation preliminary to glycogenesis. Glycogen formation via the "indirect pathway" (i.e. involving extrahepatic glycolysis, transport of lactate to the liver, and glyconeogenesis therefrom) was quantitatively insufficient to account for the observed glycogenesis. Glucokinase is contraindicated by the inverse relationship between hepatic glycogenesis and ATP availability in the ethoxyzolamide-treated preparations. In contrast, carbamyl-P:glucose phosphotransferase activity of the glucose-6-phosphatase system has the characteristics to bridge hepatic ureagenesis and glycogenesis.
Ammonium Chloride↗
Immunohistochemical localization of S-100 protein in auditory and vestibular end organs of the mouse and hamster.
The distribution of S-100-like immunoreactivity in mouse and hamster auditory and vestibular end organs was determined by the use of immunohistochemistry. Within the organ of Corti, the cytoplasm of cells of Deiter and Hensen were strongly immunoreactive. Inner hair cells and the peripheral processes and cell bodies of the spiral ganglion were weakly immunoreactive for S-100, whereas the supranuclear regions of outer hair cells and cells underlying the basilar membrane were unstained. Immunoreactivity was observed near the base of outer hair cells. In the lateral wall of the cochlea, cellular components of the spiral ligament and a subpopulation of epithelial cells in the stria vascularis, identified as predominantly basal cells, were immunoreactive. For the saccule, utricle, and semicircular canals, S-100 immunoreactivity was observed in vestibular hair cells, types I and II, and the nerve calyces surrounding type I hair cells as well as in nerve fibers underlying the sensory epithelium. Weak S-100-like immunoreactivity was associated with vestibular nerve fibers and cell bodies in the vestibular ganglion. The localization of S-100-like immunoreactivity to the sensory cells and nerve fibers of the peripheral auditory and vestibular end organs is consistent with a functional role for S-100 proteins at these sites.
Animals↗
Transmission of bovine spongiform encephalopathy to sheep and goats.
Spongiform encephalopathy has been confirmed in both 'positive' and 'negative' lines of Cheviot sheep (selected for their differential response on experimental exposure to scrapie) after intracerebral injection or oral dosing with brain homogenate derived from cattle with bovine spongiform encephalopathy (BSE). With either challenge the incubation period of the disease ranged from 440 to 994 days in both lines of sheep. In a similar experiment, three Anglo-Nubian goats developed the disease 506 to 570 days after intracerebral infection with the same BSE homogenate, and two of three goats developed the disease 941 and 1501 days after oral dosing; the other goat and some sheep from each of the experimental groups remain alive 1720 days after exposure. This is the first report of the experimental transmission of BSE to sheep and goats.
Administration, Oral↗
Conjunctival instillation of scrapie in mice can produce disease.
Mice were infected with one of two strains of scrapie by instilling brain homogenate into the conjunctiva to establish whether infection could be initiated. Of the 55 mice infected with ME7 scrapie, 23 developed clinical disease 323 +/- 8 (mean +/- standard error) days later. Three out of 12 mice infected with 79A scrapie developed disease after 232 +/- 35 days. The ME7 incubation period is similar to that for the oral route of infection. We feel that these results emphasize the need for adequate eye protection when handling tissues infected with spongiform encephalopathies.
Animals↗
Immunohistochemical localization of S-100 protein in the saccule of the rainbow trout (Salmo gairdnerii R.).
The distribution of S-100-like immunoreactivity in the trout saccule (a presumed organ of hearing in fish) has been determined by means of immunohistochemistry. Within the sensory epithelium of the saccular macula, hair cells and myelinated saccular nerve fibers were found to be immunoreactive. Hair-cell immunoreactivity was relatively uniform throughout the macula except at the extreme periphery (rostral, caudal, ventral and dorsal), where staining was either decreased or absent. The immunoreactivity associated with myelinated nerve fibers was greatest at the peripheral edges of the nerve processes, a position corresponding to the location of Schwann cells. However, the nerve processes themselves (within and subjacent to the sensory epithelium), as well as cell bodies within the saccular nerve, were also immunoreactive. Thus, the immunoreactivity of the saccular nerve observed above the basal lamina can be attributed to the saccular nerve processes as well as to nerve-associated Schwann cells. Overall, the immunoreactivity displayed by hair cells was less intense than that associated with myelinated saccular nerve, as evidenced by a disappearance of signal in hair cells first, upon serial dilution of antibody. No S-100-like immunoreactivity was observed in supporting cells within the sensory epithelium or in epithelial cells in non-sensory regions. A concentration of S-100-like immunoreactivity in hair cells and saccular nerve is suggestive of the presence of S-100 calcium-binding protein-mediated activities in these cell types.
Animals↗
Swaledale sheep affected by natural scrapie differ significantly in PrP genotype frequencies from healthy sheep and those selected for reduced incidence of scrapie.
PrP glycoprotein gene polymorphisms were examined in Swaledale sheep affected by natural scrapie, in healthy sheep and in Swaledales selected for low susceptibility to scrapie. The three groups differed significantly in frequencies of PrP genotypes detected by the restriction enzymes EcoRI, HindIII and BspHI, the latter being indicative of a PrP protein amino acid difference at codon 136. These frequency differences were confirmed in a single-flock study and present good evidence that scrapie susceptibility and resistance are associated with PrP gene variants in Swaledale sheep.
Age Factors↗
Cellular events involved in hormonal control of receptor-mediated endocytosis: regulation occurs at multiple sites in the low density lipoprotein pathway, including steps beyond the receptor.
We used biochemical and quantitative structural approaches to analyze hormonal regulation of receptor-mediated endocytosis of human low density lipoprotein (LDL) by differentiating rat granulosa cells in culture. We studied uptake and metabolism of 125I-labeled LDL and distribution of gold-labeled LDL in nontreated and FSH- or FSH/androstenedione-treated granulosa cells. FSH and androstenedione worked together to enlarge the segment of the granulosa cell population capable of accumulating LDL and to increase the number of LDL receptors at the cell surface. More importantly, FSH affected postreceptor aspects of the LDL pathway, including 1) accelerating the apparent rate of LDL internalization, and 2) decreasing the time needed for LDL to reach lysosomes. In both cases we eliminated the possibility that the observed effects merely reflected differences in receptor numbers between hormone-treated and nontreated cells. FSH also increased the number of both gold-labeled lysosomes per cellular profile and gold particles per lysosome. In all, FSH expanded the capacity of the LDL pathway to accommodate more intracellular ligand by augmenting the numbers of organelles participating in the endocytic process. However, it did not affect cell size, sizes of individual organelles comprising the LDL pathway, or numbers of gold particles per organelle (except lysosomes). Our findings indicate that hormonal regulation of the LDL pathway extends beyond simply causing expression of cell surface LDL receptors to encompass postreceptor events, including enhancing the apparent rates at which ligand is internalized and transported to lysosomes.
Androstenedione↗
Cervical cancer and health care resources in Newark, New Jersey, 1970 to 1988.
OBJECTIVES: In the past, the predominantly Black population of Newark, NJ, had little access to programs promoting or providing Pap tests. The ratio of in situ to invasive cases of cervical carcinoma was markedly reduced in all age categories, indicating inadequate screening for this cancer in this population. Funding became available to provide and publicize Pap smears but ceased after 5.5 years. We examined the effect of these changes in funding. METHODS: Data came from all Newark hospitals and practitioners and from the state cancer registry. There are now data on incidence of in situ and invasive cervical cancer in Newark from 1970 through 1988, including years before, during, and after program funding. RESULTS: The ratio of in situ to invasive cervical cancer increased and decreased in a striking parallel with the provision and subsequent cessation of funding. CONCLUSIONS: Cessation of funding of education and screening programs can result in resumption of an unfavorable in situ/invasive cervical carcinoma ratio in a poor population.
Adolescent↗
Recent advances in hepatic glucose 6-phosphatase regulation and function.
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Animals↗
Natural scrapie in British sheep: breeds, ages and PrP gene polymorphisms.
One hundred and sixty-seven sheep of 32 breeds and crossbreeds affected by natural scrapie throughout Britain were tested for the presence of restriction fragment length polymorphisms of the PrP gene observed when their DNA was digested with EcoRI or HindIII. These polymorphisms have already been associated with different susceptibilities to experimental scrapie (controlled by alleles of the Sip gene) in a flock of Cheviot sheep. In two studies 86 to 92 per cent of the sheep were found to carry the PrP gene EcoRI fragment e1 which is associated with high susceptibility (or the sA allele of Sip) to experimental scrapie. The PrP gene HindIII genotypes of the natural scrapie sheep were not apparently associated with differences in susceptibility to scrapie. There was no link between the polymorphisms and the age or breed of the affected sheep.
Age Factors↗
Studies on maternal transmission of scrapie in sheep by embryo transfer.
The technique of embryo transfer was used to investigate the maternal transmission of scrapie in sheep. Embryo donor ewes were experimentally infected with scrapie (all eventually developing the disease) and artificially inseminated six months later with semen from an uninfected scrapie-susceptible ram. Embryos were harvested five and six days after insemination and transferred by laparoscopy, unwashed, into recipient ewes which had been genetically selected for very low susceptibility to scrapie. Six of the 26 lambs born to these recipients developed scrapie.
Animals↗
Folate binding protein from kidney brush border membranes contains components characteristic of a glycoinositol phospholipid anchor.
A number of cell surface proteins have been shown to be anchored to the plasma membrane by a covalently attached glycoinositol phospholipid (GPL) in amide linkage to the C-terminus of the mature protein. We applied several criteria to establish that folate binding protein (FBP) in brush border membranes of rat kidney contains a GPL anchor. Brush border membranes were isolated and labeled with [3H]folate, and the complex of FBP and [3H]folate was shown to be released to the supernatant by incubation with purified bacterial phosphatidylinositol-specific phospholipase C (PIPLC) but not by incubation with a purified bacterial phosphatidylcholine-specific phospholipase C. The FBP-[3H]folate complex both in crude extracts and after FBP purification by ligand-directed affinity chromatography interacted with Triton X-114 micelles, and prior incubation with PIPLC prevented this detergent interaction. Individual residues characteristic of GPL anchors were found to be covalently associated with FBP following polyacrylamide gel electrophoresis in sodium dodecyl sulfate. These included glucosamine and ethanolamine, which were radiolabeled by reductive methylation and identified by chromatography on an amino acid analyzer, and inositol phosphate, which was inferred by Western blotting with an anti-CRD antisera. This antisera gave positive immunostaining only after FBP had been cleaved by PIPLC, a reliable diagnostic of a GPL anchor. The relationship between GPL-anchored FBP in biological membranes and soluble FBP in biological fluids also is discussed.
Animals↗
Glyconeogenesis from L-proline involves metabolite inhibition of the glucose-6-phosphatase system.
L-Proline's glycogenic action is unlike that of other amino acids in that it produces effects beyond those explainable by a simple increase in osmolarity (Baquet, A., Hue, L., Meijer, A. J., van Woerkom, G. M., and Plomp, P. J. A. M. (1990) J. Biol. Chem. 265, 955-959). We postulate that this effect may relate to inhibition of hepatic glucose-6-P hydrolysis by a proline-derived metabolite. We tested this hypothesis with isolated livers from rats fasted 48 h which were perfused with L-proline or L-glutamine. Net glucose and net glycogen production and levels of glucose-6-P and certain other hepatic metabolites were measured. The data obtained support our hypothesis by demonstrating fundamental differences in the metabolic fates of proline and glutamine in the liver. Both pass through alpha-ketoglutarate in the initial stage of gluconeogenesis, but proline supports hepatic glycogen formation while glutamine does not. The concomitant increase in hepatic glucose-6-P and proline-associated glyconeogenesis suggests that inhibition of glucose-6-P hydrolysis by a proline-derived metabolite may divert glucose-6-P produced from proline from glucose production and to glycogen synthesis. This conclusion is supported by the effects of perfusions with and without proline (3-mercaptopicolinate present) on (a) glyconeogenesis and glucose formation from dihydroxyacetone, (b) net glucose uptake and glycogen formation with 30 mM glucose as substrate, and (c) glucose production from endogenous glycogen in perfused livers from fed rats.
Animals↗
Ultrastructural localization of sialylated glycoconjugates in cells of the salamander olfactory mucosa using lectin cytochemistry.
An indirect gold-labeling method utilizing the lectin from Limax flavus was employed to characterize the subcellular distribution of sialic acid in glycoconjugates of the salamander olfactory mucosa. The highest density of lectin binding sites was in secretory vesicles of sustentacular cells. Significantly lower densities of lectin binding sites were found in secretory granules of acinar cells of both Bowman's and respiratory glands. Lectin binding in acinar cells of Bowman's glands was confined primarily to electron-lucent regions and membranes of secretory granules. In the olfactory mucus, the density of lectin binding sites was greater in the region of mucus closest to the nasal cavity than in that closest to the epithelial surface. At the epithelial surface, the density of lectin binding sites associated with olfactory cilia was 2.4-fold greater than that associated with microvilli of sustentacular cells or non-ciliary plasma membranes of olfactory receptor neurons, and 7.9-fold greater than non-microvillar sustentacular cell plasma membranes. Lectin binding sites were primarily associated with the glycocalyx of olfactory receptor cilia. The cilia on cells in the respiratory epithelium contained few lectin binding sites. Thus, sialylated glycoconjugates secreted by sustentacular cells are preferentially localized in the glycocalyx of the cilia of olfactory receptor neurons.
Ambystoma↗
Hysteretic behavior of the hepatic microsomal glucose-6-phosphatase system.
Carbamyl-P:glucose and PPi:glucose phosphotransferase, but not inorganic pyrophosphatase, activities of the hepatic microsomal glucose-6-phosphatase system demonstrate a time-dependent lag in product production with 1 mM phosphate substrate. Glucose-6-P phosphohydrolase shows a similar behavior with [glucose-6-P] less than or equal to 0.10 mM, but inorganic pyrophosphatase activity does not even at the 0.05 or 0.02 mM level. The hysteretic behavior is abolished when the structural integrity of the microsomes is destroyed by detergent treatment. Calculations indicate that an intramicrosomal glucose-6-P concentration of between 20 and 40 microM must be achieved, whether in response to exogenously added glucose-6-P or via intramicrosomal synthesis by carbamyl-P:glucose or PPi:glucose phosphotransferase activity, before the maximally active form of the enzyme system is achieved. It is suggested that translocase T1, the transport component of the glucose-6-phosphatase system specific for glucose-6-P, is the target for activation by these critical intramicrosomal concentrations of glucose-6-P.
Animals↗
Partial dominance of the sA allele of the Sip gene for controlling experimental scrapie.
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Alleles↗