Selection and immunomagnetic purging of peripheral blood CD34+ cells for autologous transplantation in B-cell non-Hodgkin's lymphomas

Background: Clonogenic tumor cells in the hematopoietic progenitor cell harvest may contribute to relapse after high dose therapy for B-cell malignancies. Purging of the HPC harvest requires large amounts of anti-B-cell antibodies, whereas CD34-selection enriches self renewing HPC's but malignant cells are still detectable in many CD34+ fractions. Patients and methods: We examined the feasability and safety of a CD34-selection followed by purging with anti-B-cell antibodies in 11 patients with B-cell non-Hodgkin's lymphomas undergoing high-dose therapy with cyclophospha-mide, BCNU and etoposide with retransfusion of autologous HPC's. Results: A mean number of 340 × 108 mononuclear cells was used for CD34-selection and immunomagnetic purging. CD34+ cells were enriched from a mean of 1.7% (range 0.2%-4.5%) to a mean of 68% (range 49%-87%) with a mean recovery of 27% (range 15%-43%). The mean number of retransfused CD34+ cells was 1.2× 106/kg (range 0.6-2.2 ×106/kg) body weight with a median of 11 days (range 10-13 days) to neutrophil recovery of 0.5×109/1 and 17 days (range 13-25 days) to platelet recovery of 50 × 109/1. Mean number of intravenous antibiotics and inpatient days were 8 (range 0-14) and 22 (range 19-26) respectively. Major toxicity consisted in four septicemias. Conclusions: CD34-selected and purged HPC's are safe and mediate rapid hematological recovery after high dose therapy for B-cell non-Hodgkin's lymphoma

Continuity or change in business representation in Britain? An assessment of the Heseltine initiatives of the 1990s

Britain has a fragmented, overlapping, and underresourced system of business representation. Attempts at reform, however, have proved difficult and largely unsuccessful. A coherent and logical system is relevant, in terms of both an effective dialogue between government and business, and the promotion of competitiveness and productivity. Through interviews and archival evidence, I look at how government has attempted to reform business associations. The main focus is the Heseltine initiatives of the 1990s: I outline the various initiatives taken, reveal the extent to which policy represented continuity or change, and consider whether the initiatives were effective. I show that they had a degree of success but that they would have made greater impact if they had been sustained over a longer period of time. A consideration of the historical context, moreover, suggests there may be limits to the role of government intervention in business association reform

The changing patterns of group politics in Britain

Two interpretations of ways in which group politics in Britain have presented challenges to democracy are reviewed: neo-corporatism or pluralistic stagnation and the rise of single issue interest groups. The disappearance of the first paradigm created a political space for the second to emerge. A three-phase model of group activity is developed: a phase centred around production interests, followed by the development of broadly based 'other regarding' groups, succeeded by fragmented, inner directed groups focusing on particular interests. Explanations of the decay of corporatism are reviewed. Single issue group activity has increased as party membership has declined and is facilitated by changes in traditional media and the development of the internet. Such groups can overload the policy-making process and frustrate depoliticisation. Debates about the constitution and governance have largely ignored these issues and there is need for a debate

Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells

RNA interference and the microRNA (miRNA) pathway can induce sequence-specific mRNA degradation and/or translational repression. The human genome encodes hundreds of miRNAs that can post-transcriptionally repress thousands of genes. Using reporter constructs, we observed that degradation of mRNAs bearing sites imperfectly complementary to the endogenous let-7 miRNA is considerably stronger in human HEK293 than HeLa cells. The degradation did not result from the Ago2-mediated endonucleolytic cleavage but it was Dicer- and Ago2-dependent. We used this feature of HEK293 to address the size of a pool of transcripts regulated by RNA silencing in a single cell type. We generated HEK293 cell lines depleted of Dicer or individual Ago proteins. The cell lines were used for microarray analyses to obtain a comprehensive picture of RNA silencing. The 3'-untranslated region sequences of a few hundred transcripts that were commonly up-regulated upon Ago2 and Dicer knock-downs showed a significant enrichment of putative miRNA-binding sites. The up-regulation upon Ago2 and Dicer knock-downs was moderate and we found no evidence, at the mRNA level, for activation of silenced genes. Taken together, our data suggest that, independent of the effect on translation, miRNAs affect levels of a few hundred mRNAs in HEK293 cells

Temporal characteristics of speech: The effect of age and speech style

Aging affects temporal characteristics of speech. It is still a question how these changes occur in different speech styles which require various cognitive skills. In this paper speech rate, articulation rate, and pauses of 20 young and 20 old speakers are analyzed in four speech tyles: spontaneous narrative, narrative recalls, a three-participant conversation, and reading aloud. Results show that age has a significant effect only on speech rate, articulation rate, and frequency of pauses. Speech style has a higher effect on temporal parameters than speakers’ age

Automatic memory processes in normal ageing and Alzheimer’s disease

This study examined the contribution of automatic and controlled uses of memory to stem completion in young, middle-aged and older adults, and compared these data with a study involving patients with Alzheimer’s disease (AD) who performed the same task (Hudson and Robertson, 2007). In an inclusion task participants aimed to complete three-letter word stems with a previously studied word, in an exclusion task the aim was to avoid using studied words to complete stems. Performances under inclusion and exclusion conditions were contrasted to obtain estimates of controlled and automatic memory processes using process-dissociation calculations (Jacoby, 1991). An age-related decline, evident from middle age was observed for the estimate of controlled processing, whereas the estimate of automatic processing remained invariant across the age groups. This pattern stands in contrast to what is observed in AD, where both controlled and automatic processes have been shown to be impaired. Therefore, the impairment in memory processing on stem completion that is found in AD is qualitatively different from that observed in normal ageing

Post-Retained Single Crowns versus Fixed Dental Prostheses: A 7-Year Prospective Clinical Study

Biomechanical integrity of endodontically treated teeth (ETT) is often compromised. Degree of hard tissue loss and type of final prosthetic restoration should be carefully considered when making a treatment plan. The objective of this prospective clinical trial was to assess the influence of the type of prosthetic restoration as well as the degree of hard tissue loss on 7-y clinical performance of ETT restored with fiber posts. Two groups (n = 60) were defined depending on the type of prosthetic restoration needed: 1) single unit porcelain-fused-to-metal (PFM) crowns (SCs) and 2) 3- to 4-unit PFM fixed dental prostheses (FDPs), with 1 healthy and 1 endodontically treated and fiber post-restored abutment. Within each group, samples were divided into 2 subgroups (n = 30) according to the amount of residual coronal tissues after abutment buildup and final preparation: A) >50% of coronal residual structure or B) equal to or <50% of coronal residual structure. The clinical outcome was assessed based on clinical and intraoral radiographic examinations at the recalls after 6, 12, 24, 36, 48, and 84 mo. Data were analyzed by Kaplan-Meier log-rank test and Cox regression analysis (P < 0.05). The overall 7-y survival rate of ETT restored with fiber post and either SCs or FDPs was 69.2%. The highest 84-mo survival rate was recorded in group 1A (90%), whereas teeth in group 2B exhibited the lowest performance (56.7% survival rate). The log-rank test detected statistically significant differences in survival rates among the groups (P = 0.048). Cox regression analysis revealed that the amount of residual coronal structure (P = 0.041; hazard ratio [HR], 2.026; 95% confidence interval [CI] for HR, 1.031–3.982) and the interaction between the type of prosthetic restoration and the amount of residual coronal structure (P = 0.024; HR, 1.372; 95% CI for HR, 1.042–1.806) were statistically significant factors for survival (ClinicalTrials.gov NCT01532947)

Are language production problems apparent in adults who no longer meet diagnostic criteria for attention-deficit/hyperactivity disorder?

In this study, we examined sentence production in a sample of adults (N = 21) who had had attention-deficit/hyperactivity disorder (ADHD) as children, but as adults no longer met DSM-IV diagnostic criteria (APA, 2000). This “remitted” group was assessed on a sentence production task. On each trial, participants saw two objects and a verb. Their task was to construct a sentence using the objects as arguments of the verb. Results showed more ungrammatical and disfluent utterances with one particular type of verb (i.e., participle). In a second set of analyses, we compared the remitted group to both control participants and a “persistent” group, who had ADHD as children and as adults. Results showed that remitters were more likely to produce ungrammatical utterances and to make repair disfluencies compared to controls, and they patterned more similarly to ADHD participants. Conclusions focus on language output in remitted ADHD, and the role of executive functions in language production

Analysis of S. pombe SIN protein association to the SPB reveals two genetically separable states of the SIN.

The Schizosaccharomyces pombe septation initiation network (SIN) regulates cytokinesis, and asymmetric association of SIN proteins with the mitotic spindle pole bodies (SPBs) is important for its regulation. Here, we have used semi-automated image analysis to study SIN proteins in large numbers of wild-type and mutant cells. Our principal conclusions are: first, that the association of Cdc7p with the SPBs in early mitosis is frequently asymmetric, with a bias in favour of the new SPB; second, that the early association of Cdc7p-GFP to the SPB depends on Plo1p but not Spg1p, and is unaffected by mutations that influence its asymmetry in anaphase; third, that Cdc7p asymmetry in anaphase B is delayed by Pom1p and by activation of the spindle assembly checkpoint, and is promoted by Rad24p; and fourth, that the length of the spindle, expressed as a fraction of the length of the cell, at which Cdc7p becomes asymmetric is similar in cells dividing at different sizes. These data reveal that multiple regulatory mechanisms control the SIN in mitosis and lead us to propose a two-state model to describe the SIN

Die Europäisierung der öffentlichen Aufgaben

Die zunehmende Europäisierung der öffentlichen Aufgaben ist einer der wichtigsten Trends im Wandel der Staatstätigkeit in der Bundesrepublik Deutschland und in anderen Mitgliedstaaten der Europäischen Union. In diesem Essay werden die Stufen der Europäisierung der Staatstätigkeit nachgezeichnet, in Weiterführung von Lindberg/Scheingold (1970) und Schmitter (1996) quantifiziert und hinsichtlich ihrer Kosten und ihres Nutzen erörtert. Inhalt: Stufen der Europäisierung der öffentlichen Aufgaben Der Europäisierungsgrad der öffentlichen Aufgaben von 1950 bis zum Ende des 20. Jahrhunderts Vom Nutzen und von den Kosten der Europäisierung der öffentlichen Angelegenheiten Verzeichnis der zitierten Literatu