An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin lymphoma and anaplastic large cell lymphoma.

Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30+ lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30+ diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.

Use and abuse of Pb-isotope fingerprinting technique and GIS mapping data to assess lead in environmental studies.

The danger to health, especially of young children, from lead-bearing particulates in the surface environment is still a valid concern. Given the multifaceted uses of lead today as well as historically, the sources of lead must be investigated to distinguish the etiology of lead contamination on the environment. The lead isotope finger printing technique based on isotopic ratio analyses (IRA) is one of the methods used commonly for provenancing lead sources in environmental studies throughout the world. This technique, however, has some inherited shortcomings. Therefore, caution must be used in the interpretation of the results, as this technique can lead to overestimations as well as underestimations of the true source etiology/apportionment of lead in specific environments. This paper illustrates this with some examples. Data on geographical information systems (GIS) mapping in urban regions are also presented in this paper.

Relationship between parenting behaviours and specific language impairment in children.

This study investigated the relationship between parenting behaviours and specific language impairment (SLI) in children. Using a case-control design, data on 177 kindergarten children with SLI and 925 kindergarten children who were typically developing were collected using a parental questionnaire. Parents were interviewed about parenting practices classified into the following categories: conversing with children, teaching behaviours, the child's daily routine and discipline. The results revealed that parents of children who were normally developing had engaged their children in particular conversational activities more frequently than had parents with children with SLI. Parents of children diagnosed with SLI tended to teach their children school readiness skills (the alphabet and colours) and discipline their children more frequently. These relationships continued to hold after controlling for maternal education and family economic need with the exception of teaching children colour names. The results suggested that additional investigations that examine the association between these parental behaviours and children's language status through direct observation are warranted.

Guiding language development: how African American mothers and their infants structure play interactions.

This investigation explored how African American mothers and their infants at the single-word stage of development structured their play and communicated with one another. Six mother-child dyads of low socioeconomic status (SES) and six of middle SES were observed at play. Few group differences were found, with the majority of the differences involving language behaviors. The middle-SES dyads included language goals more often in their play. Middle-SES infants initiated play verbally more frequently and produced over twice as many vocalizations as their low-SES peers. In addition, middle-SES mothers used a wider variety of words when playing with their children than their low-SES counterparts. A range of play styles was found within both groups. These were categorized into three general play styles: mothers and children actively involved in play; mothers' involvement varied; and children actively engaged and mothers attentive.

Isotopic ratio analysis in residential lead-based paint and associated surficial dust.

OBJECTIVES: This investigation assessed the contribution of lead in lead-based paint (7 samples) to lead-laden dust (8 samples) in a single suburban vacant residence using isotopic ratio analysis. METHODS: Interior/exterior lead-based paint surface concentration was measured by X-ray fluorescence while dust and scrapings were analyzed chemically for total lead content and by mass spectrometry for the associated isotopic ratios. RESULTS: Four out of 5 comparisons of paint (7 samples) and dust (8 samples) for a given location did not match isotopically. In the one location where the isotopic ratio of the paint and dust samples matched closely, some portions of the paint were not intact. One explanation for the isotopic ratio match is that the dust sample may have actually been contaminated with paint flecks. This explanation appears likely since the isotopic ratio for the lead in the dust and paint sample were not in the modern average range of US environmental lead, strongly indicating a local point source of the lead in this dust sample, namely the paint at this location. Lead dust samples whose isotopic ratio lies in the modern average range for US environmental lead cannot be correlated to the paint which is beneath them, since the isotopic ratio of lead in the dust may actually be a composite of many sources of lead over time, as suggested by an isotopic ratio in the modern average range. CONCLUSIONS: From the samples from this one house, the data dispute the contention that intact lead-based paint chalks and creates lead-contaminated dust on its surface. While leaded household dust may contribute to children's lead exposure, intact paint need not contribute to surficial lead-laden dust. Isotopic ratio measurements can be useful for point-source determination by virtue of sample match and by placement of the ratio on the spectrum of isotopic ratio values for lead. Point-source assessment based on isotopic ratio was either strengthened or weakened by placement outside or within the average range for US environmental lead, respectively.

Disfluencies in the conversations of young children who stutter: some answers about questions.

Parents of children who stutter are often advised to reduce the number of questions they ask their children. Implicit in this advice is the assumption that children who stutter will be more disfluent when answering questions. This study assessed parent-child conversational speech for 8 parent-child pairs to determine the relative amounts of disfluency in the child's responses to questions versus making assertions. Length and complexity of the children's utterances and the frequency of the parents' requests by level of demand were also evaluated. Results suggested that the responses made by the children to their parents' requests were significantly less likely to contain disfluencies than were their assertions. Also, longer and more complex utterances were more likely to contain disfluencies, regardless of their designation as assertions or responses. Parents were shown to favor request types of lower levels of demand in conversations. Requests posed with greater levels of demand were somewhat more likely to yield disfluent responses than were those at a lower demand level.

Perceived contrastive stress production in hearing-impaired and normal-hearing children.

Contrastive stress production patterns of 20 moderate-to-severely hearing-impaired children, aged 4:5-18:2 (years:months), were compared with those of 20 normal-hearing children, aged 3:7-6:7. The groups were matched on the basis of a linguistic measure, mean length of utterance. Analyses of judges' responses to the speakers' audiotapes recorded during a conversation-based task yielded evidence of similar production patterns for the groups although considerable individual performance variation was noted. This finding supports the view that language-matched normal and hearing-impaired children may not be very different in their production of this prosodic cue. Results of this study further support the idea that prosodic features of the speech signal enhance intelligibility, a factor which merits consideration in the intelligibility assessment and training of hearing-impaired children.

Linguistic and nonlinguistic features of style in normal and language-impaired children.

This study explored two questions concerning the language-learning styles described in recent investigations of early child language. The first question was whether features suggestive of language-learning style, for example, extent of pronoun use, jargon-like speech, formulaic speech, and certain play behaviors occurred in clusters consistent with the specific lexical distribution patterns of young normal children delineated by Nelson (1973). The second portion of the study addressed whether language-impaired children could be characterized as reflecting the same language-learning styles attributed to normal children. Eight children, four normally-developing and four language-impaired, were classified as "referential" or "expressive" speakers on the basis of their lexical distribution. For both the normal and language-impaired children, linguistic features suggested in the literature as correlating to one or another language-learning style were found to exist in clusters consistent with the children's pattern of lexical distribution. In addition, analyses of videotaped samples coded for the focus and context of the normal and language-impaired children's play behaviors revealed object-based and social-interaction-based activities that were generally consistent with the children's lexical distribution.

Performative and presuppositional skills in language-disordered and normal children.

The presuppositional and performative abilities of language-disordered and normal children were compared, controlling for the children's ability to use the lexical items required in the experimental tasks. Subjects were 36 children, 18 normal and 18 language-disordered, functioning at a single-word level of linguistic development. Results revealed that both the language-disordered and the normal children showed a tendency to encode changing rather than unchanging situational elements. The two groups of children also demonstrated similar levels of imperative and declarative performance intent. For both groups, performative and presuppositional behaviors were usually in the form of word productions. Discrepancies between the findings of this and other investigations are discussed with respect to the size of the children's lexicons, their expressive command of the lexicon, chronological age, and representational skills.

Inappropriate word extensions in the speech of young language-disordered children.

The purpose of this study was to determine the frequency of inappropriate word extensions in the spontaneous speech of young language-disordered children, and how these extensions should be characterized. Inappropriate word extensions were identified and tested, first in a production task and then in a comprehension task for nine language-disordered children (age 2:8 to 3:4). Results indicated that the percentage of inappropriate word extensions seen in the speech of these children was comparable to that seen in normal children at the same level of linguistic development. As with normal children, these inappropriate word extensions reflected varying levels of lexical knowledge. The findings of this study are discussed in terms of their clinical applicability for lexical training with language-disordered children.

Early lexical acquisition in children with specific language impairment.

This study examined the characteristics of early lexical acquisition in children with specific language impairment. Sixteen unfamiliar words and referents were exposed across 10 sessions to language-impaired and normal children matched for level of linguistic development. Posttesting revealed similar comprehension-production gaps in the two groups of children. In addition, both groups showed greater comprehension and production of words referring to objects than words referring to objects than words referring to actions. However, the language-impaired children's object word bias was not as marked as that of the normal children. For both groups, words containing initial consonants within the children's production repertoires were more likely to be acquired in production than words containing consonants absent from the children's phonologies. A similar tendency was not seen for comprehension.

Lyophilization of sincalide and correlation of headspace relative humidity with product stability.

An optimum freeze-drying cycle was developed for use with industrial equipment in the processing in vials of a product degraded by traces of moisture. The relative humidity of the headspace gas of the vials, which contained only 5 microgram of active ingredient, was monitored by a GC method and was then correlated with product stability.