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41.
Yucesoy B Kurzius-Spencer M Johnson VJ Fluharty K Kashon ML Guerra S Luster MI Burgess JL 《Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine》2008,50(6):642-648
OBJECTIVE:: To investigate whether genetic variants involved in cytokine expression are associated with the age-related rate of decline in forced expiratory volume in 1 second (FEV1). METHODS:: Functional polymorphisms in the TNFalpha, TGFbeta1, IL-1beta, IL-1RN, IL-13, and IL-8 genes were investigated in 374 active firefighters with at least five pulmonary function tests. RESULTS:: A protective effect was found between the presence of the TGFbeta1 -509 TT genotype and rate of decline in FEV1 (P = 0.043). Carrying an A allele at TNFalpha -308 (P = 0.010) and GG genotype at TNFalpha -238 (P = 0.028) was associated with a more rapid rate of FEV1 decline. The TNFalpha -308A/-238G haplotype was also associated with an increased rate of decline as compared with the other haplotypes. CONCLUSIONS:: Interindividual variability in progressive decline in FEV1 may be explained in part by genetic variations within genes involved in inflammatory responses. 相似文献
42.
Berran Yucesoy Victor J. Johnson Kara Fluharty Michael L. Kashon James E. Slaven Nevin W. Wilson David N. Weissman Raymond E. Biagini Dori R. Germolec Michael I. Luster 《Vaccine》2009
The magnitude of the immune response to vaccinations can be influenced by genetic variability. In the present study, we aimed to investigate whether cytokine or cytokine receptor gene polymorphisms were associated with variations in the immune response to childhood vaccination. The study group consisted of 141 healthy infants who had been immunized with hepatitis B vaccine (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using a 5′ nuclease PCR assay. Post vaccination total, isotypic, and antigen-specific serum antibody levels were measured using multiplex immunoassays. Significant associations were observed between SNPs in the TNFα, IL-12B, IL-4Rα, and IL-10 genes and vaccine-specific immune responses (p < 0.05). In addition, SNPs in the IL-1β, TNFα, IL-2, IL-4, IL-10, IL-4Rα, and IL-12B genes were associated with variations in serum levels of immunoglobulins (IgG, IgA, IgM) and IgG isotypes (IgG1–IgG3) (p < 0.05). These data suggest that genetic variations in cytokine genes can influence vaccine-induced immune responses in infants, which in turn may influence vaccine efficacy. 相似文献
43.
S J Fluharty L E Rabow M J Zigmond E M Stricker 《The Journal of pharmacology and experimental therapeutics》1985,235(2):354-360
Subtotal destruction of central noradrenergic neurons with the neurotoxin, 6-hydroxydopamine, is known to increase tyrosine hydroxylase (TH) activity within surviving nerve terminals. The present report demonstrates a similar, dose-related elevation of TH activity in the adrenal medulla and sympathetic nerves after systemic 6-hydroxydopamine treatment. Two temporally distinct processes were observed in the sympathetic nerves: a rapid activation of TH, present during the first few days after the lesion, and a more gradual increase in maximal TH activity, most probably due to enzyme induction. In this regard, the stimulatory effect on catecholamine biosynthesis of cyclic AMP-dependent phosphorylation was attenuated substantially within cardiac sympathetic nerves 3 days after the lesion, but by 3 weeks the efficacy of cyclic AMP-dependent phosphorylation was restored completely. Similarly, the normal activation of cardiac TH activity elicited by insulin-induced hypoglycemia and cold stress was absent soon after 6-hydroxydopamine treatment, but returned 3 weeks later. These latter findings suggest that the adaptations within the sympathoadrenal system after subtotal sympathectomy can preclude further adaptations to stress. 相似文献
44.
45.
Fluharty CB Johnson J Whitelegge J Faull KF Fluharty AL 《Journal of neuroscience research》2001,63(1):82-89
Cerebroside sulfate activator (saposin B) is a small protein involved in glycosphingolipid metabolism. It binds certain membrane lipids, making them available to water-soluble enzymes. Defects in this protein are responsible for a form of metachromatic leukodystropy, a progressive neurodegenerative condition. The protein participates in the catabolism of a number of lipids but does show lipid binding selectivity. However, the basis of this selectivity is unclear. Here we assess the relative binding of a number of lipids compared to cerebroside sulfate (sulfatide). We utilize a competitive binding paradigm, in which the lipids compete for protein under favorable conditions and are then switched to a condition in which the complex is stable. This study is unique in that a single molecular species of the activator is employed, and an expanded selection of natural and semisynthetic membrane lipids is surveyed. No simple "binding rule" can be ascertained from these data, but ligands with longer and/or more complex lipoidal and polar adducts appear to be favored. 相似文献
46.
Arvan L. Fluharty Lee Neidengard David Holtzman Hayato Kihara 《Metabolic brain disease》1986,1(3):187-195
Clinical and biochemical findings in a male subject with progressive encephalopathy and peripheral neuropathy are presented. Early development was normal. At age 3.5 years, he had seizures associated with fever. Subsequently, there was progressive neurologic deterioration. A CT brain scan at age 4 years, 2 months demonstrated multiple areas of variable density in the white matter. There was mild slowing of nerve conduction velocities and a sural nerve biopsy revealed segmentai demyelinative neuropathy. Metachromatic leukodystrophy was suspected, but arylsulfatase A activity in leukocytes and fibroblasts was in the normal range. The cerebroside sulfate loading test on intact cultured fibroblasts showed attenuated hydrolysis leading to a tentative diagnosis of cerebroside sulfatase activator deficiency. However, the attenuated response of proband fibroblasts was not normalized by supplementation with activator in a reproducible manner, and urine showed hyperexcretion rather than deficiency of activator. Ultimately, an assay for galactosylceramide/gb-galactosidase activity established a deficiency of this enzyme leading to the diagnosis of late-onset Krabbe disease. 相似文献
47.
Angiotensin II plays a key role in the regulation of body fluid homeostasis. To correct body fluid deficits that occur during hypovolaemia, an animal needs to ingest both water and electrolytes. Thus, it is not surprising that angiotensin II, which is synthesized in response to hypovolaemia, acts centrally to increase both water and NaCl intake. Here, we review findings relating to the properties of angiotensin II receptors that give rise to changes in behaviour. Data are described to suggest that divergent signal transduction pathways are responsible for separable behavioural responses to angiotensin II, and a hypothesis is proposed to explain how this divergence may map onto neural circuits in the brain. 相似文献
48.
49.
KM, a single 23-year-old male, sustained a severe traumatic brain injury in a motor vehicle accident. Aggressive and uncooperative behaviour, resulting from the client's cognitive deficits and hypersensitivity to stimuli, made him unmanageable in a subacute rehabilitation setting. Minimizing sources of agitation reduced the client's outbursts and facilitated the completion of functional tasks, such as bathing and dressing. Modifying his environment also increased the client's participation in social and leisure activities. These changes improved the outcome of the client's rehabilitation. 相似文献
50.
Angiotensin and mineralocorticoids, the hormones of sodium conservation, acted together to arouse a sodium appetite with shorter latency and greater magnitude than is produced by larger amounts of each acting alone. This potentiation was selective for sodium ingestion and occurred in the absence of significant changes in sodium balance. Therefore, because endogenous angiotensin and mineralocorticoids are concurrently elevated during sodium deficiency, sodium appetite may be aroused by a synergy of the peptide and the steroid. 相似文献