CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb, Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC acid MCC, we wished to determine if this was also the case in MCC, Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and I on 9p. No loss of heterozygosity (LO H) was peen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p, Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined, Half of all informative cases had LOH at D95168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168, A second region (InFNA-D9S126) showed L0H in 10(44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all Il tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p 14' antibody, These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus. (C) 2001 Wiley-Liss, Inc.

Language and disability in Japan

Language relating to disability in the public arena has been a sensitive issue in Japan as elsewhere. Since the 1970s and 80s, major media organisations have replaced words considered derogatory with more acceptable equivalents; laws, statutes and other legal documents have likewise been revised. This article examines how the language used to portray people with disabilities has changed, how the changes came about and how they were received. The debate has largely been played out in four public spaces, which to some extent intersect and overlap: the media (both print and visual), the laws, literature and, increasingly now, the Internet. I argue that while the laws were rewritten primarily as the result of external international trends, such as the International Year of Disabled Persons, disability groups achieved media compliance mainly by exploiting the keen desire of Japanese media organisations to avoid public embarrassment resulting from vocal protests over infractions.

Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension

Pulmonary vascular remodeling is an important pathological feature of pulmonary hypertension, leading to increased pulmonary vascular resistance and reduced compliance. It involves thickening of all three layers of the blood vessel wall (due to hypertrophy and/or hyperplasia of the predominant cell type within each layer), as well as extracellular matrix deposition. Neomuscularisation of non-muscular arteries and formation of plexiform and neointimal lesions also occur. Stimuli responsible for remodeling involve transmural pressure, stretch, shear stress, hypoxia, various mediators [angiotensin II, endothelin (ET)-1, 5-hydroxytryptamine, growth factors, and inflammatory cytokines], increased serine elastase activity, and tenascin-C. In addition, there are reductions in the endothelium-derived antimitogenic substances, nitric oxide, and prostacyclin. Intracellular signalling mechanisms involved in pulmonary vascular remodeling include elevations in intracellular Ca2+ and activation of the phosphatidylinositol pathway, protein kinase C, and mitogen-activated protein kinase. In animal models of pulmonary hypertension, various drugs have been shown to attenuate pulmonary vascular remodeling. These include angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, ET receptor antagonists, ET-converting enzyme inhibitors, nitric oxide, phosphodiesterase 5 inhibitors, prostacyclin, Ca2+-channel antagonists, heparin, and serine elastase inhibitors. Inhibition of remodeling is generally accompanied by reductions in pulmonary artery pressure. The efficacy of some of the drugs varies, depending on the animal model of the disease. In view of the complexity of the remodeling process and the diverse aetiology of pulmonary hypertension in humans, it is to be anticipated that successful anti-remodeling therapy in the clinic will require a range of different drug options. (C) 2001 Elsevier Science Inc. All rights reserved.

MapScript: A map algebra programming language incorporating neighborhood analysis

Map algebra is a data model and simple functional notation to study the distribution and patterns of spatial phenomena. It uses a uniform representation of space as discrete grids, which are organized into layers. This paper discusses extensions to map algebra to handle neighborhood operations with a new data type called a template. Templates provide general windowing operations on grids to enable spatial models for cellular automata, mathematical morphology, and local spatial statistics. A programming language for map algebra that incorporates templates and special processing constructs is described. The programming language is called MapScript. Example program scripts are presented to perform diverse and interesting neighborhood analysis for descriptive, model-based and processed-based analysis.

Using a cartographic modeling language to manipulate spectral satellite imagery

Land related information about the Earth's surface is commonIJ found in two forms: (1) map infornlation and (2) satellite image da ta. Satellite imagery provides a good visual picture of what is on the ground but complex image processing is required to interpret features in an image scene. Increasingly, methods are being sought to integrate the knowledge embodied in mop information into the interpretation task, or, alternatively, to bypass interpretation and perform biophysical modeling directly on derived data sources. A cartographic modeling language, as a generic map analysis package, is suggested as a means to integrate geographical knowledge and imagery in a process-oriented view of the Earth. Specialized cartographic models may be developed by users, which incorporate mapping information in performing land classification. In addition, a cartographic modeling language may be enhanced with operators suited to processing remotely sensed imagery. We demonstrate the usefulness of a cartographic modeling language for pre-processing satellite imagery, and define two nerv cartographic operators that evaluate image neighborhoods as post-processing operations to interpret thematic map values. The language and operators are demonstrated with an example image classification task.

The English-only movement: A communication analysis of changing perceptions of language vitality

This paper reexamines the potential impact of the English-only movement on linguistic minorities and Anglos' perceptions of their own and minority groups' language vitality. Of particular interest is the Hispanic population-the fastest growing minority in the U.S. Communication scholars have paid only scant attention to the English-only movement and how it affects the social and communication climate for Latinos. However, literature reviews prepared for the American Psychological Association and for the Teachers of English to Speakers of Other Languages (in 1991 and 1995, respectively) concluded that English-only initiatives have negative consequences for limited-English proficiency groups. Revisiting this still-growing issue in the light of more recent studies across disciplines and media reports, we examine how Anglo support for English-only policies limits the use, promotion, and salience of minority languages like Spanish in institutional settings and in the linguistic landscape and suggest directions for future research.

Incremental parsing in language-based editors: user needs and how to meet them

Incremental parsing has long been recognized as a technique of great utility in the construction of language-based editors, and correspondingly, the area currently enjoys a mature theory. Unfortunately, many practical considerations have been largely overlooked in previously published algorithms. Many user requirements for an editing system necessarily impact on the design of its incremental parser, but most approaches focus only on one: response time. This paper details an incremental parser based on LR parsing techniques and designed for use in a modeless syntax recognition editor. The nature of this editor places significant demands on the structure and quality of the document representation it uses, and hence, on the parser. The strategy presented here is novel in that both the parser and the representation it constructs are tolerant of the inevitable and frequent syntax errors that arise during editing. This is achieved by a method that differs from conventional error repair techniques, and that is more appropriate for use in an interactive context. Furthermore, the parser aims to minimize disturbance to this representation, not only to ensure other system components can operate incrementally, but also to avoid unfortunate consequences for certain user-oriented services. The algorithm is augmented with a limited form of predictive tree-building, and a technique is presented for the determination of valid symbols for menu-based insertion. Copyright (C) 2001 John Wiley & Sons, Ltd.

Social cognition, language acquisition and the development of the theory of mind

Theory of Mind (ToM) is the cognitive achievement that enables us to report our propositional attitudes, to attribute such attitudes to others, and to use such postulated or observed mental states in the prediction and explanation of behavior. Most normally developing children acquire ToM between the ages of 3 and 5 years, but serious delays beyond this chronological and mental age have been observed in children with autism, as well is in those with severe sensory impairments. We examine data from Studies of ToM in normally developing children and those with deafness, blindness, autism and Williams syndrome, as well as data from lower primates, in a search for answers to key theoretical questions concerning the origins, nature and representation of knowledge about the mind. In answer to these, we offer a framework according to which ToM is jointly dependent upon language and social experience, and is produced by a conjunction of language acquisition with children's growing social understanding, acquired through conversation and interaction with others. We argue that adequate language and adequate social skills are jointly causally sufficient, and individually causally necessary, for producing ToM. Thus our account supports a social developmental theory of the genesis of human cognition, inspired by the work of Sellars and Vygotsky.

Dipeptidyl peptidase IV is a target for covalent adduct formation with the acyl glucuronide metabolite of the anti-inflammatory drug zomepirac

The nonsteroidal anti-inflammatory drug zomepirac (ZP) is metabolised to a chemically reactive acyl glucuronide conjugate (ZAG) which can form covalent adducts with proteins. In vivo, such adducts could initiate immune or toxic responses. In rats given ZP, the major band detected in liver homogenates by immunoblotting with a polyclonal ZP antiserum was at 110 kDa. This adduct was identified as ZP-modified dipeptidyl peptidase IV (DPP IV) by immunoblotting using the polyclonal ZP antiserum and monoclonal DPP IV antibodies OX-61 and 236.3. In vitro, ZAG, but not ZP itself, covalently modified recombinant human and rat DPP IV. Both monoclonal antibodies recognized DPP IV in livers from ZP- and vehicle-dosed rats. Confirmation that the 110 kDa bands which were immunoreactive with the ZP and DPP IV antibodies represented the same molecule was obtained from a rat liver extract reciprocally immunodepleted of antigens reactive with these two antibodies. Furthermore, immunoprecipitations with OX-61 antibody followed by immunolotting with ZP antiserum, and the reciprocal experiment, showed that both these antibodies recognised the same 110 kDa molecule in extracts of ZP-dosed rat liver. The results verify that DPP IV is one of the protein targets for covalent modification during hepatic transport and biliary excretion of ZAG in rats. (C) 2001 Elsevier Science Inc. All rights reserved.