Sp1 phosphorylation regulates inducible expression of platelet-derived growth factor B-chain gene via atypical protein kinase C-ζ

Platelet-derived growth factor (PDGF) is a broadly expressed mitogenic and chemotactic factor with diverse roles in a number of physiologic and pathologic settings. The zinc finger transcription factors Sp1, Sp3 and Egr-1 bind to overlapping elements in the proximal PDGF B-chain promoter and activate transcription of this gene. The anthracycline nogalamycin has previously been reported to inhibit the capacity of Egr-1 to bind DNA in vitro. Here we used electrophoretic mobility shift assays to show that nogalamycin added to cells in culture did not alter the interaction of Egr-1 with the PDGF-B promoter. Instead, it enhanced the capacity of Sp1 to bind DNA. Nogalamycin increased PDGF-B mRNA expression at the level of transcription, which was abrogated by mutation of the Sp1 binding site in the PDGF-B promoter or overexpression of mutant Sp1. Rather than increasing total levels of Sp1, nogalamycin altered the phosphorylation state of the transcription factor. Overexpression of dominant-negative PKC-ζ blocked nogalamycin-inducible Sp1 phosphorylation and PDGF-B promoter-dependent expression. Nogalamycin stimulated the phosphorylation of PKC-ζ (on residue Thr410). These findings demonstrate for the first time that PKC-ζ and Sp1 phosphorylation mediate the inducible expression of this growth factor.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Series for atypical children.

v. 1a. A number story book -- v. 1b. A number sotry book (loose leaf) -- v. 2. Blank book -- v. 3. Sentence game no. 1 -- v. 4. Word dominoes.

Resting energy expenditure is lower than predicted in people taking atypical antipsychotic medication

Resting energy expenditure (REE) is lower than predicted in persons taking atypical antipsychotic medication, and weight management is a significant clinical challenge for some of them. However, to date there have been no published guidelines to assist clinicians in choosing appropriate prediction equations to estimate energy expenditure in persons taking atypical antipsychotic medications. The objectives of this study were to measure REE in a group of men taking the atypical antipsychotic clozapine and to determine whether REE can be accurately predicted for this population using previously published regression equations. REE was measured using indirect calorimetry via a ventilated hood on eight men who had completed at least 6 months of treatment with clozapine. Comparisons between measured REE and predicted REE using five different equations were undertaken. The commonly-used Harris-Benedict and Schofield equations systematically overestimated REE. Predictions of REE from other equations were too variable for clinical use. When estimating energy requirements as part of a weight-management program in men who have been taking clozapine for 6 months, predictions of REE from the equations of Harris-Benedict and Schofield should be reduced by 280 kcal/day.

Atypical prostatic glandular proliferations on needle biopsy - Diagnostic implications, use of immunohistochemistry, and clinical significance

In recent times, PSA screening and a substantial increase in prostate needle biopsies have not only resulted in detection of minute foci of cancer but have also very likely resulted in increased detection of atypical glandular proliferations. Not uncommonly, there are only a limited number of atypical glands in these biopsies, and these require careful evaluation to enable an accurate diagnosis. We describe diagnostic implications, use of immunohistochemistry, and clinical significance of these lesions. Foci of atypical glands, also labeled atypical small acinar proliferation of uncertain significance, have features suspicious for but not diagnostic of cancer. Atypical foci include a broad group of lesions of differing clinical significance. These include benign, small acinar proliferations mimicking prostate cancer and atypical glandular proliferations suspicious for carcinoma. Definite diagnosis requires accurate histopathologic assessment and judicious use of immunohistochemistry. Patients with atypical glands on prostate needle biopsy have a high risk for harboring cancer and therefore have an increased risk for having cancer detected in subsequent biopsies.

What nominal phrases are all about: the atypical case of indefinite pronouns with a determiner

This paper presents novel data that challenge the traditional categorial understanding of the nominal phrase. The established use of an indefinite pronoun with a determiner in French (ce quelqu'un, du n'importe quoi, un je ne sais quoi) contravenes assumptions both about pronouns, which should not be embedded, and nominal phrases, which should be headed by a noun. Analysed here for the first time, the embedding of a pronoun under a determiner is shown to find its justification in the semantic import of the construction. The anaphoric role guaranteeing referential continuity is promoted by a strong determiner; weak determiners typically contribute to constructing a designative use of the pronoun when a more precise characterisation cannot or will not be provided. How this construction would be analysed in the Minimalist Programme is presented to suggest that the phrase satisfies semantic requirements, which resolves the paradoxes of its traditional definition

The atypical bilingual courtroom:an exploratory study of the interactional dynamics in interpreter-mediated trials in Hong Kong

This study investigates the communication process in the atypical bilingual Hong Kong courtroom, where, unlike in most other jurisdictions, interpreting services are routinely provided for the linguistic majority instead of the linguistic minority and the interpreter usually has to work with court actors who share his/her bilingual knowledge. It sets out to explore how the unique nature of the bilingual Hong Kong courtroom impacts on interactional dynamics in communicative process in the courtroom and potentially on the administration of justice, using authentic recordings of nine criminal trials from three court levels, supplemented by a survey administered to court interpreters. It compares the participant roles of different court actors in different court settings, monolingual and bilingual, using Goffman’s (1981) participation framework and Bell’s (1984) audience design as the conceptual framework. It is found that the notion of recipientship in the atypical bilingual Hong Kong courtroom is complicated by the presence of other bilinguals, which inevitably changes the interactional dynamics and impacts on the power of court interpreter as these bilinguals take on more participant roles in the process. The findings of this study show that the power of court actors is realised in the participant role(s) they and the other co-present court actors take on or are capable of playing. The findings also indicate that a change in the participant role of a court actor has an impact on the participation status other actors, which may in turn hamper the administration of justice. It is also found that the notion of power asymmetry in the courtroom has an effect on the footings adopted by the interpreter and thus on his/her neutrality. This thesis identifies training needs and makes recommendations for best practice in the courtroom and for institutional administrative practice.

Atypical connectivity in autistic spectrum disorders

Autism is a developmental disorder that is currently defined in terms of a triad of impairments in social interaction, communication, and behavioural flexibility. Psychological models have focussed on deficits in high level social and cognitive processes, such as ‘weak central coherence’ and deficits in ‘theory of mind’. Converging evidence from different fields of neuroscience research indicates that the underlying neural dysfunction is associated with atypical patterns of cortical connectivity (Rippon et al., 2007). This arises very early in development and results in sensory, perceptual and cognitive deficits at a much earlier and more fundamental level than previously suggested, but with cascading effects on higher level psychological and social processes. Earlier research in this sphere has focussed mainly on patterns of underconnectivity in distributed cortical networks underpinning process such as language and executive function. (Just et al., 2007). Such research mainly utilises imaging techniques with high spatial resolution. This paper focuses on evidence associated with local over-connectivity, evident in more low level and transitory processes and hence more easily measurable with techniques with high temporal resolution, such as MEG and EEG. Results are described which provide evidence of such local over-connectivity, characterised by atypical results in the gamma frequency range (Brown et al., 2005) together with discussions about the future directions of such research and its implications for remediation.

Clinical utility of amyloid PET imaging in the differential diagnosis of atypical dementias and its impact on caregivers

La maladie d’Alzheimer (MA) se caractérise pathologiquement par l’accumulation de plaques amyloïde dans le cerveau. La tomographie par émission de positrons (TEP) permet d’imager les plaques amyloïde in vivo. Le but de ce projet est d’évaluer le rôle de la TEP amyloïde dans le processus diagnostique de la MA dans des cas de démences atypiques. Le deuxième but de ce projet est de déterminer l’impact de la révélation d’un diagnostic plus certain chez les proches aidants. 28 patients sans diagnostic malgré une investigation exhaustive ont été sélectionnées et imagées avec le traceur amyloïde 18F-NAV4694 (âge 59,3 ans, é-t. 5,8; MMSE 21.4, é-t 6.0). Les neurologues référents documentaient par la suite tout changement de niveau de certitude, de diagnostic, de traitement et/ou de prise en charge. Les proches aidants consentants ont été rencontrés subséquemment, et un questionnaire avec une échelle de Likert a été utilisé afin de documenter l’impact de l’imagerie leur perception de la maladie. Notre cohorte a été également divisée entre amyloïde positifs (14/28) et négatifs (14/28). Un changement de diagnostic a lieu dans 9/28 cas (32,1% :17.8% ont changé de MA à non-MA, 14,3% de non-MA à MA). Il y avait une augmentation significative (p<0,05) de 44% dans la certitude du neurologue suite à cet examen. Un changement de prise en charge a été obtenu dans 20/28 (71,4%) des cas. Bien que non significatifs statistiquement, un impact favorable sur les proches-aidants a été noté. Cette étude suggère que l’imagerie amyloïde a un rôle bénéfique dans les cas de démences atypiques n’ayant pu être élucidés avec les techniques d’investigations actuellement recommandées. De plus, le processus a été perçu positivement par les proches aidants, notamment en encourageant du temps de qualité avec leurs personnes chères. Ceci illustre un rôle prometteur des biomarqueurs, qui sont de plus en plus explorés.

Management and follow-up of a patient with Familial Atypical Multiple Mole-Melanoma (FAMMM) Syndrome

Introduction. Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is an autosomal dominant genodermatosis characterized by the presence of a high number of dysplastic nevi and family history of melanoma or pancreatic cancer. Melanomas in FAMMM patients tend to occur at a younger age, although they are clinically similar to sporadic melanomas in terms of overall survival. Case report. A 45 year-old woman with a family history of melanoma, a type II phototype and numerous (>100) nevi was admitted to our Department of Dermatology and Plastic Surgery. Over the past years, the patient underwent several surgical operations to remove pigmented lesions and two are dysplastic nevi. Since 1995, she underwent surgery to remove four melanomas. She is followed for skin examinations including dermoscopy. Conclusion. Identifying high-risk patients for melanoma represents a primary objective for the specialists that are involved in the management of this disease, especially in order to enact all the necessary surveillance and follow-up strategies.