Biomedical subjects

Nadine Martin

Publications and source records attributed to Nadine Martin.

13 recordsLinked to original sources

PubMed2006

Small-cell lung carcinoma of recipient origin after bilateral lung transplantation for cystic fibrosis.

Bronchial carcinoma, usually of the non-small-cell type, is uncommon after lung transplantation and occurs predominantly in single-lung transplant ex-smoker recipients on their native lung. Bronchial carcinoma of donor origin is much rarer. We report the case of a small-cell lung carcinoma of recipient origin that occurred 12 months after a bilateral lung transplantation for cystic fibrosis in a 25-year-old woman who was a non-smoker. The tumor was of recipient origin, due to a gender mismatch between donor and recipient. This unusual observation corroborates the hypothesis of chimerism of the bronchial epithelium after lung transplantation.

Adult↗

PubMed2006

The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis.

Cellular senescence and apoptosis have evolved to restrain unwarranted proliferation of potentially tumorigenic cells. Here we show that overexpression of the E3 SUMO ligase PIASy in normal human fibroblasts recruits the p53 and Rb tumor suppressor pathways to provoke a senescence arrest. By contrast, in Rb-deficient fibroblasts, expression of PIASy leads to p53-dependent apoptosis. Induction of senescence requires PIASy E3 activity and is specific for this member of the PIAS ligase family. PIASy stimulates sumoylation and transcriptional activity of p53 and increases Rb-dependent corepression through recruitment to E2F-responsive promoters. Viral oncoprotein E6 suppresses both PIASy-induced senescence and sumoylation of PIASy substrates. Finally, we show that fibroblasts lacking PIASy exhibit a highly reduced propensity to undergo senescence in response to a prosenescence stimulus. Altogether, these data provide the first evidence for a direct role of an E3 SUMO ligase, and by implication of the SUMO pathway, in cellular senescence and apoptosis.

Apoptosis↗

PubMed2006

Effectiveness of contextual repetition priming treatments for anomia depends on intact access to semantics.

Naming of two semantically impaired aphasic patients was treated with the contextual repetition priming technique, which involves repeated repetition of names of pictures that are related semantically, phonologically, or are unrelated. Our previous studies using this technique have suggested that patients with impaired access to lexical-semantic representations benefit in the short-term from this treatment technique, but show no long-term improvement in naming. In contrast, patients with good access to semantics show short- and long-term benefits from this treatment. Here we report two studies of treatment for two individuals with aphasia affecting access to lexical semantics and anomia but spared access to input and output phonology and spared conceptual semantics. We predicted that they would show short-term facilitation from the contextual priming, but no long-term improvements in naming. The results confirmed the prediction. An account of this pattern is offered within the framework of an interactive activation model of word retrieval. Additionally, we discuss alternative techniques for addressing naming deficits when access to semantics is impaired.

Adult↗

PubMed2006

Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL): a new diagnostic marker providing evidence that AITL derives from follicular helper T cells.

Angioimmunoblastic T-cell lymphoma (AITL) represents a distinct entity among peripheral T-cell lymphomas (PTCLs). The cellular origin of AITL remains unknown, although a possible derivation from follicular helper T cells (TFH) has been suggested based on the CD4/Bcl-6 phenotype. It has been recently shown that expression of CXCL13, a chemokine critically involved in B-cell migration into germinal centers, is characteristic of TFH cells, as compared with other T helper subsets. We compared CXCL13 expression in 29 AITLs, 20 PTCLs, unspecified, 10 anaplastic large cell lymphomas (ALCL), and 4 other PTCLs. We showed that CXCL13 is expressed by AITL (29 of 29, 100%) and a subset of PTCL, unspecified (6 of 20, 30%), which all showed borderline features with AITL, but in only 1 of 10 (10%) ALCLs, and 0 of 4 other PTCLs. Two-color immunostainings further showed that CXCL13 was found in the cytoplasm of atypical CD5-positive T cells that expressed CD10. We conclude that CXCL13 expression is a common characteristic of AITL, which can help to delineate the morphologic spectrum of the disease, and further supports its derivation from TFH cells. CXCL13 expression may also provide an additional useful tool for the diagnosis of AITL.

Aged↗

PubMed2005

Contextual priming in semantic anomia: a case study.

The present case continues the series of anomia treatment studies with contextual priming (CP), being the second in-depth treatment study conducted for an individual suffering from semantically based anomia. Our aim was to acquire further evidence of the facilitation and interference effects of the CP treatment on semantic anomia. Based on the results of the study of , our hypothesis before the treatment was that our participant would show short-term interference and at most modest and short-term benefit from treatment. To acquire such evidence would not only be important for the choice of anomia treatment methods in individual patients, but would also prompt further development of the CP method. The CP technique used for our participant included cycles of repeating and naming items in three contextual conditions (semantic, phonological, and unrelated). As predicted, the overall improvement of naming was modest and short-term. Interestingly, the contextual condition that corresponded with the nature of our patient's underlying naming deficit (semantic) elicited immediate interference in the form of contextual naming errors, as well as short-term improvement of naming. Based on this and a recent study by , it appears that despite short-term positive effects, in its current form the CP treatment is not sufficient for those aphasics who have a semantic deficit underlying their anomia. The possible mechanism and directions for future research are discussed.

Aged↗

PubMed2004

Measurements of auditory-verbal STM span in aphasia: effects of item, task, and lexical impairment.

In the first part of this study, we investigated effects of item and task type on span performance in a group of aphasic individuals with word processing and STM deficits. Group analyses revealed significant effects of item on span performance with span being greater for digits than for words. We also investigated associations between subjects' lexical-semantic and phonological processing abilities and performance on four measures of verbal span (digit and word span, each varied for type of response, verbal vs. pointing) as well as one measure of nonverbal span. We predicted and found that the patterns of association between verbal span tasks and lexical abilities reflected the integrity of language processes and representations deployed in each paradigm used to assess span. Performance on the pointing span task, which engages both lexical-semantic and phonological processes, correlated with measures of both lexical-semantic and phonological abilities. Performance on repetition span, which engages primarily input and output phonological processes, correlated with measures of phonological abilities but not measures of lexical-semantic abilities. However, when partial correlations were performed for two subject groups based on their relative preservation of lexical-semantic ability (less or more than phonological ability), repetition span correlated with lexical-semantic measures only in the subgroup with relatively impaired lexical-semantics. Additionally, performance on the nonverbal span task correlated with measures of phonological abilities, suggesting either a general cognitive deficit affecting verbal and nonverbal STM or possibly, the use of a verbal strategy to perform this task. Our discussion focuses on the interpretation of span measurements in clinical practice and research, as well as the implications of these data for theories of short-term memory and word processing.

Adult↗

PubMed2004

Learning new names for new objects: cortical effects as measured by magnetoencephalography.

We tracked the evolvement of naming-related cortical dynamics with magnetoencephalography when five normal adults successfully learned names and/or meanings of unfamiliar objects. In all subjects, the learning of new names was associated with pronounced cortical effects. The learning effect was of long latency and emerged as a change of activation in the same cortical network that was active during naming of familiar items. In four out of five subjects, the cortical learning effect occurred in the inferior parietal lobe. In three of these subjects, the cortical effect was left-sided. These results suggest that the inferior parietal lobe plays an important role in the acquisition of novel words, presumably as a part of working memory systems.

Adult↗

PubMed2004

Profiles of the 2 INK4a gene products, p16 and p14ARF, in human reference urothelium and bladder carcinomas, according to pRb and p53 protein status.

The INK4a/ARF locus encodes 2 cell cycle regulatory proteins: p16 and p14(ARF). P16 inhibits the activities of cdks, which maintain the retinoblastoma protein (pRb) in its active hypophosphorylated state. P14(ARF) blocks MDM2-induced p53 degradation and transactivational silencing. In this study, we investigated the expression of p16 and p14(ARF) in reference human urothelium and in 51 urothelial carcinomas (UCs) of all stages and grades, by reverse transcription-polymerase chain reaction (RT-PCR). Patterns of p14(ARF) and p16 expression were compared with each other and then with patterns of p53 and pRb protein expression, respectively, as determined by immunohistochemistry. P14(ARF) and p16 mRNAs were present at low levels or were undetectable in reference urothelia and in most superficial tumors, whereas they were present at high levels in a subset of tumors of advanced stage and high grade. The expression profiles of these 2 mRNAs were correlated in all but 4 cases, indicating that the 2 INK4a products may have nonredundant functions. Forty-six of the 51 tumors (90%) presented changes to or a lack of activation of the p14(ARF)-p53 pathway and were p53 positive (n = 10), p14(ARF) negative (n = 23), or both p53 positive and p14(ARF) negative (n = 13), suggesting that these 2 components of the pathway may be altered or nonactivated. Markedly high levels of p16 mRNA (n = 5) were associated with the absence of pRb expression, with the exception of 1 case in which the p16 gene contained a deletion mutation. A lack of p16 mRNA or low levels of this mRNA were associated with pRb detection in all but 1 case. In invasive UCs, the p16-pRb pathway, the p14(ARF)-p53 pathway, or in many cases both pathways were altered or not activated, demonstrating the involvement of these pathways in invasive bladder tumorigenesis.

Carcinoma↗

PubMed2004

Expression of stromal cell-derived factor-1 and of its receptor CXCR4 in liver regeneration from oval cells in rat.

Stromal cell-derived factor-1 is a chemokine that plays a major role during embryogenesis. Since stromal cell-derived factor-1 and its unique receptor CXCR4 are involved in the differentiation of progenitor cells, we studied the expression of this chemokine and of its receptor in hepatic regeneration from precursor oval cells. Hepatic regeneration was induced by treating rats with 2-acetylaminofluorene, and followed by partial hepatectomy. Oval cell accumulation, which predominated in periportal regions, reached a maximum at days 9 to 14 after hepatectomy and declined thereafter. Oval cells strongly expressed stromal cell-derived factor-1 protein and mRNA. CXCR4 mRNA hepatic level paralleled the number of oval cells and in situ hybridization showed CXCR4 mRNA expression by these cells. Treatment of rats with fucoidan, a sulfated polysaccharide which binds to stromal cell-derived factor-1 and blocks its biological effects, markedly decreased oval cell accumulation in five of the seven treated rats. In conclusion, our data demonstrate an expression of stromal cell-derived factor-1 and of its receptor CXCR4 in oval cells during hepatic regeneration and strongly suggest that stromal cell-derived factor-1 stimulates the proliferation of these precursor cells through an autocrine/paracrine pathway.

2-Acetylaminofluorene↗

PubMed2004

Perseverations and anticipations in aphasia: primed intrusions from the past and future.

In this article, we review an account of movement errors that is based on a model of serial order and an interactive spreading activation model of word production. This account makes two claims. First, anticipations and perseverations arise from malfunctions of a mechanism that maintains serial order in speech production and that has three components: (1) a means to turn off past utterances, (2) a means to activate the present utterance (3) a means to prime the future utterance. Second, the probabilities of such movement errors are further determined by the same variables that influence the production of ordinary word and sound substitutions, such a frequency and feature overlap. We review relevant studies of movement errors produced by aphasic and nonaphasic individuals and make suggestions for further investigation of these phenomena.

Aphasia↗

PubMed2004

Space aliens and nonwords: stimuli for investigating the learning of novel word-meaning pairs.

We describe a set of pictorial and auditory stimuli that we have developed for use in word learning tasks in which the participant learns pairings of novel auditory sound patterns (names) with pictorial depictions of novel objects (referents). The pictorial referents are drawings of "space aliens," consisting of images that are variants of 144 different aliens. The auditory names are possible nonwords of English; the stimulus set consists of over 2,500 nonword stimuli recorded in a single voice, with controlled onsets, varying from one to seven syllables in length. The pictorial and nonword stimuli can also serve as independent stimulus sets for purposes other than word learning. The full set of these stimuli may be downloaded from www.psychonomic.org/archive/.

Auditory Perception↗

PubMed2003

Adult brain plasticity elicited by anomia treatment.

We describe a study where a specific treatment method for word-finding difficulty (so-called contextual priming technique, which combines massive repetition priming with semantic priming) was applied with three chronic left hemisphere-damaged aphasics. Both before and after treatment, which focused on naming of a series of pictures, naming-related brain activity was measured by magnetoencephalography (MEG). Due to its excellent temporal resolution and good spatial resolution, we were able to track treatment-induced changes in cortical activity. All three subjects showed improved naming of the trained items. In all subjects, a single source area, located in the left inferior parietal lobe, close to the lesioned area, displayed statistically significant training-induced changes. This effect was of long latency as it started 300-600 msec after picture presentation. The change in activation was specific to training, as it could not be accounted for by variation of cortical dynamics associated with increased proportion of correct answers. Our interpretation is that the training effect reflects more effective phonological encoding and storage of the trained items through the engagement of a left hemispheric word-learning system. This is in line with recent functional imaging studies, which have linked left inferior parietal lobe activity to the phonological storage component of the verbal working memory, as well as with theoretical arguments stating that the primary role of the phonological loop is to acquire new words. Finally, the MEG results showed no evidence of increased right hemisphere participation following training, supporting the view that restoration of language-related networks in the damaged left hemisphere is crucial for anomia recovery.

Aphasia↗

PubMed2003

Naming multiple objects: neural correlates as measured by positron emission tomography.

The aim of this study was to examine the neural substrates of multi-object naming by positron emission tomography in normals. Multi-object naming is used in a technique called contextual priming (CP) to elicit contextual effects on picture naming through systematic manipulation of the relatedness of to-be-named pictures in an array. Inhibitory and facilitatory effects of CP on naming have been used both to highlight the inner dynamics of the normal word retrieval system and to treat naming difficulties caused by acquired anomia. Because of the complexity of the CP technique, it is unclear whether it merely reflects lexical retrieval or whether it also recruits general cognitive resources such as attentional control and response selection to a significant degree. When compared with a baseline situation in which colored circles were named, multi-object naming elicited increased blood flow in the occipital lobe and in the left inferior temporal and fusiform gyri. These areas have been related to visual pattern recognition and semantic access, and the pattern of activation is in line with previous functional imaging studies on single picture naming. In conclusion, multi-object naming does not appear to activate brain regions beyond those needed for single object naming. These findings thus provide independent evidence for the claim that CP is a valid paradigm for the study of word production proper.

Adult↗