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Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies.

Wilson, C B; Westall, J; Johnston, L; Lewis, D B; Dower, S K; Alpert, A R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1986 Português
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Human neonatal lymphocytes produced little macrophage activation factor in response to mitogens. This correlated with decreased production of interferon-gamma (IFN gamma): adult lymphokines contained 894.2 +/- 177.1 U/ml, whereas neonatal cord and peripheral lymphokines contained 66.9 +/- 17.0 and 116.7 +/- 29.6 U/ml by bioassay. Results by radioimmunoassay (RIA) for IFN gamma were similar. In contrast, the interleukin 2 content of cord lymphokines was greater (P less than 0.01) and that of neonatal peripheral blood lymphokines similar to that of adults. Interleukin 1 production and interleukin 2 receptor expression and affinity were similar for adult and neonatal cells. Interleukins 1 and 2 in amounts comparable to those in adult lymphokines did not increase production of macrophage activation factor or IFN gamma by neonatal cells. Neonatal cells did not contain intracellular IFN or degrade exogenous IFN. Excess suppressor activity was not found in neonatal cultures. Addition of IFN alpha, 10,000-50,000 U/ml of interleukin 2 or phorbol myristate acetate (PMA) to cord mononuclear cells or of adult monocytes or PMA to cord T cells increased IFN gamma production compared to cells stimulated with concanavalin A (ConA) alone. Nevertheless...

Alanine-261 in intracellular loop III of the human gonadotropin-releasing hormone receptor is crucial for G-protein coupling and receptor internalization.

Myburgh, D B; Millar, R P; Hapgood, J P
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/05/1998 Português
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Gonadotropin-releasing hormone (GnRH) is a decapeptide that regulates reproductive function via binding to the GnRH receptor, which is a G-protein-coupled receptor (GPCR). For several members of this family, the C-terminal domain of intracellular loop III is important in ligand-mediated coupling to G-proteins; mutations in that region can lead to constitutive activity. A specific alanine residue is involved in certain GPCRs, the equivalent of which is Ala-261 in the GnRH receptor. Mutation of this residue to Leu, Ile, Lys, Glu or Phe in the human GnRH receptor did not result in constitutive activity and instead led to complete uncoupling of the receptor (failure to support GnRH-stimulated inositol phosphate production). When this residue was mutated to Gly, Pro, Ser or Val, inositol phosphate production was still supported. All the mutants retained the ability to bind ligand, and the affinity for ligand, where measured, was unchanged. These results show that Ala-261 cannot be involved in ligand binding but is critical for coupling of the receptor to its cognate G-protein. Coupling is also dependent on the size of the residue in position 261. When the amino acid side chain has a molecular mass of less than 40 Da efficient coupling is still possible...

Genetic Overlap between Apparently Sporadic Motor Neuron Diseases

van Blitterswijk, Marka; Vlam, Lotte; van Es, Michael A.; van der Pol, W-Ludo; Hennekam, Eric A. M.; Dooijes, Dennis; Schelhaas, Helenius J.; van der Kooi, Anneke J.; de Visser, Marianne; Veldink, Jan H.; van den Berg, Leonard H.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 14/11/2012 Português
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Progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) are devastating motor neuron diseases (MNDs), which result in muscle weakness and/or spasticity. We compared mutation frequencies in genes known to be associated with MNDs between patients with apparently sporadic PMA and ALS. A total of 261 patients with adult-onset sporadic PMA, patients with sporadic ALS, and control subjects of Dutch descent were obtained at national referral centers for neuromuscular diseases in The Netherlands. Sanger sequencing was used to screen these subjects for mutations in the coding regions of superoxide dismutase-1 (SOD1), angiogenin (ANG), fused in sarcoma/translated in liposarcoma (FUS/TLS), TAR DNA-binding protein 43 (TARDBP), and multivesicular body protein 2B (CHMP2B). In our cohort of PMA patients we identified two SOD1 mutations (p.D90A, p.I113T), one ANG mutation (p.K17I), one FUS/TLS mutation (p.R521H), one TARDBP mutation (p.N352S), and one novel CHMP2B mutation (p.R69Q). The mutation frequency of these genes was similar in sporadic PMA (2.7%) and ALS (2.0%) patients, and therefore, our findings demonstrate a genetic overlap between apparently sporadic PMA and ALS.

Analysis of using Fleet Readiness Centers Vice Civilian Contractors for aircraft modification work

McKernan, Bryan T.; Herrmann, R. Erik
Fonte: Monterey California. Naval Postgraduate School Publicador: Monterey California. Naval Postgraduate School
Formato: xvi, 66 p.; 28 cm.
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MBA Professional Report; Fleet Readiness Center Southwest (FRCSW) conducts maintenance on various aircraft platforms. In addition to regular aircraft overhauls, FRCSW has the capacity to perform aircraft modifications, which are currently completed by contractors. This project examines why the FRC's are not getting more CH-53E modification work when they have the capacity and capability to complete the work. This project uses FRCSW as a case study to address the issue. Interviews were conducted with the heads of Multi-line Division within FRCSW in San Diego, California and the Commander of FRC's and the H-53 Assistant Program Manager for Logistics at Naval Air Systems Command (NAVAIR), Patuxent River, Maryland. The results of these interviews provided an assessment of the actions taken to reduce inefficiencies and non-value added activities and insight into how NAVAIR selects between contractors and FRC's to complete modification work. The data reveal that FRCSW has the capacity to complete modification work on CH-53 aircraft without schedule slippage. Also, a comparison of labor rate, schedule, and location of work, demonstrates how much more expensive FRCSW is and why NAVAIR chooses the lower cost contractor to complete modification work.