Polymerase chain reaction amplification analyses of clonality in T-cell malignancy including peripheral T-cell lymphoma

Clonality in T-cell malignancy was investigated using T-cell receptor (TcR) V beta 1-20 family primers and polymerase chain reaction amplification (PCR) of cDNA prepared from tissue biopsies and blood involved with tumour. Secondary PCR amplification of the VDJ joints of primary PCR products was performed to distinguish clonal from polyclonal products, and clonal V beta gene products were confirmed by direct PCR sequencing in the majority of cases. In eight T-cell malignancies including T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell chronic lymphocytic leukaemia (T-CLL) shown to be clonal by Southern blot analysis, one or two primary PCR products were identified and shown to be clonal. In five cases of peripheral T-cell lymphoma (PTCL) all V beta 1-20 families were identified after primary PCR amplification, and clonal products were identified in two cases after secondary amplification; TcR V beta clonal families could not be demonstrated in the remaining three cases. These data were in agreement with previous Southern blot analysis of these cases, and confirmed the presence of reactive T cells in PTCL as well as providing further evidence for the genotypic heterogeneity of this entity. In the remaining case, a blood lymphocytosis, primary PCR amplification produced predominant TcR V beta 6 and V beta 12 family products, of which the V beta 6 family proved clonal after secondary PCR amplification. There was no evidence for overrepresentation of TCR V beta families by the tumour populations in this study, furthermore the data confirm the involvement of reactive cells in T-cell malignancy and the genetic heterogeneity of PTCL.     

Constructing inferences during narrative text comprehension.

Describes a constructionist theory that accounts for the knowledge-based inferences that are constructed when readers comprehend narrative text. Readers potentially generate a rich variety of inferences when they construct a referential situation model of what the text is about. The proposed constructionist theory specifies that some, but not all, of this information is constructed under most conditions of comprehension. The distinctive assumptions of the constructionist theory embrace a principle of search (or effort) after meaning. According to this principle, readers attempt to construct a meaning representation that addresses the reader's goals, that is coherent at both local and global levels, and that explains why actions, events, and states are mentioned in the text. This study reviews empirical evidence that addresses this theory and contrasts it with alternative theoretical frameworks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Accommodation of a D-Phe residue into a right-handed 3(10)-helix: structure of Boc-D-Phe-(Aib)4-Gly-L-Leu-(Aib)2-OMe, an analogue of the amino terminal segment of antiamoebins and emerimicins

Recently an unstable trinucleotide CTG repeat, located within the 3' untranslated region of a gene on 19q13.3 was discovered in kindreds with myotonic dystrophy (DM). The age-of-onset/severity of DM shows a good correlation with CTG repeat size, and pedigrees and data reported to date have shown a striking trend toward amplification of the size of the CTG repeat during transmission from parent to child. The amplification has been accepted as the biological explanation for anticipation in the clinical severity observed in many families with DM. In this paper we report on 3 families where CTG amplification decreased during transmission from parent to child. In one case there was a gene conversion event, while in the remaining 2 there was a simpler reduction in the size of the repeat length. The changes appear to have been accompanied by a reduction in clinical severity in the child when compared to the parent. These observations are discussed in terms of their clinical implications and the biases that may exist in much of the reported data.     

Identification of potent P2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate

1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3. Monophosphate analogues that were the most potent activators of the C6 cell P2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate were potent P2Y-purinoceptor agonists no effect of these analogues on the human P2U-purinoceptor were observed. 5. These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P2Y-purinoceptors, and provide insight for strategies for development of novel P2Y-purinoceptor agonists of high potency and selectivity.     

A PET study of the neural systems of stuttering

The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.     

Negative affective consequences of thinking about disease detection behaviors.

It was proposed that thinking about disease-detection behavior would lead to more negative moods than thinking about health-promotion behavior. Detection behaviors produce more negative moods because they can threaten perceptions of good health. In a laboratory study, the initial mood states of 121 participants recruited from undergraduates and the general community were measured using a neutral-words rating procedure. Then participants were randomly assigned to think about performing a disease-detection behavior or a health-promotion behavior. Subsequently, they wrote down their responses to the behavior and evaluated these 35 either positive, negative, or neutral. Finally, the participant's mood was remeasured using both a neutral words-rating procedure and a more traditional bipolar rating measure. Results indicated that thought about disease-detection behavior produced more negative affective responses and more negative mood change than did thought about health-promotion behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improvement options for a former water-driven-mill building now used as a theatre

After investigating the financial feasibility (and so abandoning the idea) of providing self-generated electricity using hydro-power, it was recommended that the top priority should be the direct connection of an electricity supply, from the mains grid to the building; this would cost £8800. Thereby, the theatre would receive a relatively unrestricted supply of electricity at cheaper unit tariffs. This improvement should be followed by the most urgent repairs being carried out to the building fabric, at an estimated cost of £6990. These repairs are necessary to ensure the continued integrity of the building's structure, thereby inhibiting the on-going deterioration.

The energy and financial appraisal also suggested a priority listing of overall improvements to the building in order to achieve a significant, economically justifiable reduction in energy demand; the recommended options are estimated to cost in total £39819. However, the capital cost of such an upgrading would only be recouped, and the theatre achieve a sustainable future, if the building were to be used more intensively and for a wider range of activities than at present in order to increase its revenue significantly.

All prices as stated are those at August 1991.     

Electrical qualification of new ultrathin integration techniques

The aim of this paper is to analyze the feasibility of ultrathin packages through the electrical qualification of the technological process used, i.e. mechanical lapping. It considers polysilicon bipolar transistors which thickness can reach values lower than 10 μm. Forward mode and reverse mode characterizations show no significant degradation of pertinent characteristics, thus allowing to find applications in new compact packaging concept.