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991.
RG Strauss ; GA Ludwig ; MV Smith ; PJ Villhauer ; MJ Randels ; A Smith-Floss ; TA Koerner 《Transfusion》1994,34(2):116-121
BACKGROUND: Historically, paid blood donors were found to transmit hepatitis at higher rates than volunteers. In those older studies, paid donors frequently were recruited from prisons or slum areas–a finding consistent with the belief that monetary payment in itself did not necessarily lead to the high-risk status of commercial blood. Instead, it was the population base from which the donors were recruited that was important. STUDY DESIGN AND METHODS: Today, cytapheresis donors are in great demand. Because payment is one incentive that might entice donors to undertake the increased commitment of repeated cytapheresis donation, the results were studied of infectious disease history and laboratory testing performed concurrently in 917 volunteer whole-blood donors and 1240 paid cytapheresis donors, who were enrolled in distinct programs at the DeGowin Blood Center from October 7, 1987, through November 30, 1990. RESULTS: When first, repeat, and overall donations made by these donors were evaluated separately, paid cytapheresis donors were found to exhibit no increase in infectious disease history or test results beyond those of volunteer whole-blood donors. CONCLUSION: Thus, paid cytapheresis donors, when managed within a formal program, should not necessarily be presumed to be more dangerous than volunteers, from an infectious disease aspect. However, definitive proof of safety (comparison of transfusion-transmitted infection rates in two groups of patients receiving blood components exclusively from either paid cytapheresis or volunteer donors) was not pursued by long- term follow-up studies. 相似文献
992.
Suzanne ABM Aarts Tom TP Seijkens Pascal JH Kusters Claudia M van Tiel Myrthe E Reiche Myrthe den Toom Linda Beckers Cindy PAA van Roomen Menno PJ de Winther Gijs Kooij Esther Lutgens 《The Journal of pathology》2019,247(4):471-480
The costimulatory CD40L–CD40 dyad plays a major role in multiple sclerosis (MS). CD40 is highly expressed on MHCII+ B cells, dendritic cells and macrophages in human MS lesions. Here we investigated the role of the CD40 downstream signaling intermediates TNF receptor-associated factor 2 (TRAF2) and TRAF6 in MHCII+ cells in experimental autoimmune encephalomyelitis (EAE). Both MHCII–CD40–Traf2−/− and MHCII–CD40–Traf6−/− mice showed a reduction in clinical signs of EAE and prevented demyelination. However, only MHCII–CD40–Traf6−/− mice displayed a decrease in myeloid and lymphoid cell infiltration into the CNS that was accompanied by reduced levels of TNF-α, IL-6 and IFN-γ. As CD40–TRAF6 interactions predominantly occur in macrophages, we subjected CD40flflLysMcre mice to EAE. This myeloid-specific deletion of CD40 resulted in a significant reduction in EAE severity, reduced CNS inflammation and demyelination. In conclusion, the CD40–TRAF6 signaling pathway in MHCII+ cells plays a key role in neuroinflammation and demyelination during EAE. Concomitant with the fact that CD40–TRAF6 interactions are predominant in macrophages, depletion of myeloid CD40 also reduces neuroinflammation. CD40–TRAF6 interactions thus represent a promising therapeutic target for MS. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. 相似文献
993.
Statistical analysis of the effects of common chemical substituents on ligand potency 总被引:1,自引:0,他引:1
The results of a statistical analysis of more than 84,000 compounds from lead optimization programs against 30 different protein targets is presented, with a focus on the effects that different chemical substituents have on compound potency. It is observed that the potency changes induced by most chemical groups follows a nearly normal distribution centered near zero (i.e., no effect on potency). However, the widths of the distributions vary significantly between different substituents, and these effects cannot be rationalized by simple physicochemical parameters. In addition, certain substituents consistently bias the distribution toward higher or lower potency, suggesting the existence of preferred and nonpreferred chemical groups for lead optimization. The implications of these results for understanding protein-ligand recognition and for enhancing the efficiency and speed of lead optimization will be discussed. 相似文献
994.
Ogilvie N Thom Gerben Keijzers David McD Taylor Daniel M Fatovich Daniel P Finucci Jeremy Furyk Sang‐won Jin Stephen PJ Macdonald Hugh MA Mitenko Joanna R Richardson Joseph YS Ting Clinton R Gibbs Dane R Chalkley 《Emergency medicine Australasia : EMA》2016,28(5):603-606
This perspective article summarises the experience of conducting a multicentre research project. We describe expected and unexpected hurdles we experienced as well as suggesting possible solutions for researchers embarking on multicentre studies. 相似文献
995.
996.
Objective: To determine the feasibility of using a biomarker panel of myoglobin, creatinine kinase MB (CK‐MB) and cardiac troponin I (cTnI) to identify patients with suspected acute coronary syndrome (ACS) who are suitable for discharge within 2 h. Methods: We took blood at presentation and at 2 h from patients with suspected ACS and non‐diagnostic electrocardiogram who were admitted to the ED short stay ward for serial electrocardiogram and troponin testing. We used a point‐of‐care device that gives rapid estimation of myoglobin, CK‐MB and cTnI (Triage cardiac panel). These results were compared with the results of our standard hospital cardiac troponin T assay. Patients were followed up by telephone at 30 days. Results: The study group comprised 100 patients (61 men) with mean age of 58 years. Six had a troponin‐positive ACS during their ED stay. One additional patient died of a myocardial infarction within the follow‐up period. The Triage panel at 2 h after presentation predicted 12‐h cardiac troponin T elevation (sensitivity 100%, negative predictive value 99%) and 30‐day events (sensitivity 86%, negative predictive value 97%). The majority of patients were ultimately suitable for discharge. Conclusion: Serial myoglobin, CK‐MB and cTnI have the potential to identify patients who are suitable for early discharge and outpatient work‐up. A large multicentre study is required. 相似文献
997.
Detection of drug-dependent, platelet-reactive antibodies by antigen- capture ELISA and flow cytometry 总被引:7,自引:0,他引:7
The effectiveness of flow cytometry in the detection of drug-dependent, platelet-reactive antibodies was investigated. In studies of seven sera known to contain quinine- or quinidine-dependent, platelet-reactive antibodies, flow cytometry was 5 to 10 times more sensitive in detecting drug-dependent antibodies (DDAbs) than the 51Cr release assay, antigen-capture enzyme-linked immunosorbent assay (ELISA), and indirect immunofluorescence microscopic assay. With flow cytometry, DDAbs could be detected at drug concentrations as low as 0.1 microM, or less than one-tenth the level required with other methods. Antigen-capture ELISA was not as sensitive as flow cytometry in DDAb detection, but it did allow identification of the DDAbs' target molecules. With this assay, five of the seven DDAbs recognized both the glycoprotein Ib/IX (GPIb/IX) and glycoprotein IIb/IIIa (GPIIb/IIIa) complexes, while the remaining two sera reacted only with GPIb/IX. Of 44 consecutive patients who developed thrombocytopenia while taking quinidine, DDAbs were detected by flow cytometry in 11 (25%), more than twice the number detected by other methods. In one patient who developed thrombocytopenia while taking trimethoprim/sulfamethoxazole, DDAbs could be detected only by flow cytometry. It can be concluded that flow cytometry is highly sensitive in detecting DDAbs and allows their detection at pharmacologic concentrations of the drug. Most quinidine-dependent antibodies recognize at least two different glycoprotein complexes in the platelet membrane. 相似文献
998.
The spectrum of mutations in UBE3A causing Angelman syndrome 总被引:5,自引:1,他引:4
Fang P; Lev-Lehman E; Tsai TF; Matsuura T; Benton CS; Sutcliffe JS; Christian SL; Kubota T; Halley DJ; Meijers-Heijboer H; Langlois S; Graham JM Jr; Beuten J; Willems PJ; Ledbetter DH; Beaudet AL 《Human molecular genetics》1999,8(1):129-135
Angelman syndrome (AS) is characterized by mental retardation, absence of
speech, seizures and motor dysfunction. AS is caused by maternal deletions
for chromosome 15q11-q13, paternal uniparental disomy (UPD), imprinting
defects or loss-of-function mutations in the UBE3A locus which encodes
E6-AP ubiquitin-protein ligase. The UBE3A gene is imprinted with paternal
silencing in human brain and similar silencing of the Ube3a locus in
Purkinje cells and hippocampal neurons in the mouse. We have sequenced the
major coding exons for UBE3A in 56 index patients with a clinical diagnosis
of AS and a normal DNA methylation pattern. The analysis identified
disease-causing mutations in 17 of 56 patients (30%) including 13
truncating mutations, two missense mutations, one single amino acid
deletion and one stop codon mutation predicting an elongated protein.
Mutations were identified in six of eight families (75%) with more than one
affected case, and in 11 of 47 isolated cases (23%); no mutation was found
in one family with two siblings, one with a typical and one with an
atypical phenotype. Mutations were de novo in nine of the 11 isolated
cases. An amino acid polymorphism of threonine substituted for alanine at
codon 178 was identified, and a 3 bp length polymorphism was found in the
intron upstream of exon 8. In all informative cases, phenotypic expression
was consistent with imprinting with a normal phenotype when a mutation was
on the paternal chromosome and an AS phenotype when a mutation was on the
maternal chromosome. Laboratory diagnosis and genetic counseling for AS are
complex, and mutation analysis is valuable in clinically typical AS
patients with a normal methylation analysis.
相似文献
999.
Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent's disease 总被引:16,自引:1,他引:15
Devuyst O; Christie PT; Courtoy PJ; Beauwens R; Thakker RV 《Human molecular genetics》1999,8(2):247-257
Dent's disease, which is a renal tubular disorder characterized by low
molecular weight proteinuria, hypercalciuria and nephrolithiasis, is
associated with inactivating mutations of the X-linked chloride channel,
CLC-5. However, the manner in which a functional loss of CLC-5 leads to
such diverse renal abnormalities remains to be defined. In order to
elucidate this, we performed studies to determine the segmental expression
of CLC-5 in the human kidney and to define its intracellular distribution.
We raised and characterized antisera against human CLC-5, and identified by
immunoblotting an 83 kDa band corresponding to CLC-5 in human kidney cortex
and medulla. Immunohistochemistry revealed CLC-5 expression in the
epithelial cells lining the proximal tubules and the thick ascending limbs
of Henle's loop, and in intercalated cells of the collecting ducts. Studies
of subcellular human kidney fractions established that CLC-5 distribution
was associated best with that of Rab4, which is a marker of recycling early
endosomes. In addition, confocal microscopy studies using the proximal
tubular cell model of opossum kidney cells, which endogenously expressed
CLC-5, revealed that CLC-5 co-localized with the albumin- containing
endocytic vesicles that form part of the receptor-mediated endocytic
pathway. Thus, CLC-5 is expressed at multiple sites in the human nephron
and is likely to have a role in the receptor-mediated endocytic pathway.
Furthermore, the functional loss of CLC-5 in the proximal tubules and the
thick ascending limbs provides an explanation for the occurrences of low
molecular weight proteinuria and hypercalciuria, respectively. These
results help to elucidate further the patho-physiological basis of the
renal tubular defects of Dent's disease.
相似文献
1000.