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991.
992.
A Valsamakis H Schneider PG Auwaerter H Kaneshima MA Billeter DE Griffin 《Canadian Metallurgical Quarterly》1998,72(10):7754-7761
An understanding of the determinants of measles virus (MV) virulence has been hampered by the lack of an experimental model of infection. We have previously demonstrated that virulence phenotypes in human infections are faithfully reproduced by infection of human thymus/liver (thy/liv) implants engrafted into SCID mice, where the virus grows primarily in stromal cells but induces thymocyte apoptosis (P. G. Auwaerter et al., J. Virol. 70:3734-3740, 1996). To begin to elucidate the roles of the C protein, V protein, and the 5' untranslated region of the F gene (F 5'UTR) in MV infection in vivo, the replication of strains bearing mutations of these genes was compared to that of the parent sequence-tagged Edmonston strain (EdTag). Growth curves show that mutants fall into two phenotypic classes. One class of mutants demonstrated kinetics of growth similar to that of EdTag, with decreased peak titers. The second class of mutants manifested peak titers similar to that of EdTag but had different replication kinetics. Abrogation of V expression led to delayed and markedly prolonged replication. Additionally, thymocyte survival was prolonged and implant architecture was preserved throughout the course of infection. In contrast, massive bystander thymocyte death occurred after infection with EdTag and all other mutants. A mutant which overexpressed V in Vero cells (V+) had the opposite phenotype of the A mutant not expressing V (V-). V+ grew more rapidly than EdTag with 100-fold-greater levels of virus production 3 days after infection. These results suggest that C, V, and the F 5'UTR are accessory factors required for efficient virus replication in vivo. In addition, thymocyte survival after V- infection suggests this protein may play multiple roles in pathogenesis of MV infection of thymus. Since these recombinant mutant viruses grew identically to the parent virus in Vero cells, the data show that thy/liv implants are an excellent model for investigating the determinants of MV virulence. 相似文献
993.
MH Fisher AM Amend TJ Bach JM Barker EJ Brady MR Candelore D Carroll MA Cascieri SH Chiu L Deng MJ Forrest B Hegarty-Friscino XM Guan GJ Hom JE Hutchins LJ Kelly RJ Mathvink JM Metzger RR Miller HO Ok ER Parmee R Saperstein CD Strader RA Stearns DE MacIntyre 《Canadian Metallurgical Quarterly》1998,101(11):2387-2393
Activation of beta3 adrenergic receptors on the surface of adipocytes leads to increases in intracellular cAMP and stimulation of lipolysis. In brown adipose tissue, this serves to up-regulate and activate the mitochondrial uncoupling protein 1, which mediates a proton conductance pathway that uncouples oxidative phosphorylation, leading to a net increase in energy expenditure. While chronic treatment with beta3 agonists in nonprimate species leads to uncoupling protein 1 up-regulation and weight loss, the relevance of this mechanism to energy metabolism in primates, which have much lower levels of brown adipose tissue, has been questioned. With the discovery of L-755,507, a potent and selective partial agonist for both human and rhesus beta3 receptors, we now demonstrate that acute exposure of rhesus monkeys to a beta3 agonist elicits lipolysis and metabolic rate elevation, and that chronic exposure increases uncoupling protein 1 expression in rhesus brown adipose tissue. These data suggest a role for beta3 agonists in the treatment of human obesity. 相似文献
994.
Q Zeng VN Subramaniam SH Wong BL Tang RG Parton S Rea DE James W Hong 《Canadian Metallurgical Quarterly》1998,9(9):2423-2437
cDNA clones encoding a novel protein (VAMP5) homologous to synaptobrevins/VAMPs are detected during database searches. The predicted 102-amino acid VAMP5 harbors a 23-residue hydrophobic region near the carboxyl terminus and exhibits an overall amino acid identity of 33% with synaptobrevin/VAMP1 and 2 and cellubrevin. Northern blot analysis reveals that the mRNA for VAMP5 is preferentially expressed in the skeletal muscle and heart, whereas significantly lower levels are detected in several other tissues but not in the brain. During in vitro differentiation (myogenesis) of C2C12 myoblasts into myotubes, the mRNA level for VAMP5 is increased approximately 8- to 10-fold. Immunoblot analysis using antibodies specific for VAMP5 shows that the protein levels are also elevated approximately 6-fold during in vitro myogenesis of C2C12 cells. Indirect immunofluorescence microscopy and immunoelectron microscopy reveal that VAMP5 is associated with the plasma membrane as well as intracellular perinuclear and peripheral vesicular structures of myotubes. Epitope-tagged versions of VAMP5 are similarly targeted to the plasma membrane. 相似文献
995.
DE Wilcken 《Canadian Metallurgical Quarterly》1998,168(9):431-432
Teeth agenesis is an anomaly of frequent observation with a familiar heredity transmission pattern. In a frequency order the most common agenetic teeth are: third molars, upper lateral incisors and second lower bicuspids. Of exceptional rarity is the absence of second molars. Our observation confirm the heredity pattern of congenitally missing permanent teeth; in this case anomaly showed variable expressivity and different degree of severity. 相似文献
996.
DE Stanczak 《Canadian Metallurgical Quarterly》1998,8(4):191-201
Several obstacles exist that impede the scientific study of pathological underarousal (stupor and coma). For instance, there is a lack of a clear, rational, standardized taxonomy with which to describe the phenomenon. Moreover, there is considerable confusion of the construct of arousal with other neurobehavioral constructs. The field also suffers from a general lack of acceptably reliable and valid instruments, especially measures of long-term outcome. Additionally, current treatments for chronic pathological underarousal are frequently presumptive and applied haphazardly, and thus do little to elucidate the process of recovery. It is suggested that biomedical and neuropsychological approaches to the study and treatment of pathological underarousal are complementary and that it is useful to view pathological underarousal as a behavioral, as well as a medical, phenomenon. 相似文献
997.
998.
M Jaksch S Hofmann S Kleinle S Liechti-Gallati DE Pongratz J Müller-H?cker KB Jedele T Meitinger KD Gerbitz 《Canadian Metallurgical Quarterly》1998,35(11):895-900
COX deficiency is believed to be the most common defect in neonates and infants with mitochondrial diseases. To explore the causes of this group of disorders, we examined 25 mitochondrial genes (three COX subunit genes and 22 tRNA genes) and 10 nuclear COX subunit genes for disease associated mutations using PCR-SSCP and direct sequencing of polymorphic SSCP fragments. DNA from one patient with severe COX deficiency and with consanguineous parents was entirely sequenced. The patient population consisted of 21 unrelated index patients with mitochondrial disorders and predominant (n=7) or isolated (n=14) COX deficiency. We detected two distinct tRNA(Ser)(UCN) mutations, which have been recently described in single kindreds, in a subgroup of four patients with COX deficiency, deafness, myoclonic epilepsy, ataxia, and mental retardation. Besides a number of nucleotide variants, a single novel missense mutation, which may contribute to the disease phenotype, was found in the mitochondrial encoded COX 1 gene (G6480A). Mutations in nuclear encoded COX subunit genes were not detected in this study. 相似文献
999.
1000.
Two acrylic cube phantoms have been constructed for BNCT applications that allow the depth distribution of neutrons to be measured with miniature 10BF3 detectors in 0.5-cm steps beginning at 1-cm depth. Sizes and weights of the cubes are 14 cm, 3.230 kg, and 11 cm, 1.567 kg. Tests were made with the epithermal neutron beam from the patient treatment port of the Brookhaven Medical Research Reactor. Thermal neutron depth profiles were measured with a bare 10BF3 detector at a reactor power of 50 W, and Cd-covered detector profiles were measured at a reactor power of 1 kW. The resulting plots of counting rate versus depth illustrate the dependence of neutron moderation on the size of the phantom. But more importantly the data can serve as benchmarks for testing the thermal and epithermal neutron profiles obtained with accelerator-based BNCT facilities. Such tests could be made with these phantoms at power levels about five orders of magnitude lower than that required for the treatment of patients with brain tumors. 相似文献