bluuebunny/crossref_metadata_2025 huggingface dataset:
Phonologically Delayed Children's Responses To Three Types of Pictured Stimuli
Authors: Bernthal John E. , Grossman Fred M. , Aerts Goll Annette E.
Published: December 2008

The purpose of this study was to examine 18 phonologically delayed children's (aged 6 years, 0 months to 7 years, 6 months) responses to three types of pictured stimuli (black and white line drawings, colored line drawings, and colored photographs). The size of pictures, coloration of the pictures, number of target items presented per card, surface or gloss of the pictures, and the number of items pictured on each card were similar across the three sets of stimuli. The only difference among the three sets of pictured stimuli was the method of pictorial representation. Results indicated that there was a statistically significant difference between the number of correct identifications to black and white line drawings and the colored line drawings and colored photographs.
The Authenticity of Ethnographic Research
Authors: Maxwell Madeline M.
Published: December 2008

In this introduction to this special publication of JCCD, the principles of ethnography are explained and placed within the domain of social research. Issues such as the role of interpretation in science, the balance of subjectivity and objectivity in social research, and beliefs about science in American culture all contribute to the evaluation of qualitative research in general and ethnographic research in particular The value of ethnographies for clinicians and teachers as well as researchers is addressed in an overview of the papers that follow.
A Retrospective Examination of Interactional Behaviors Viewed as Experimentally Nonsignificant
Authors: Prelock Patricia A.
Published: December 2008

In the process of field testing a metalinguistic intervention procedure, unanticipated behaviors were noted. Although these behaviors did not have a statistically significant impact on the results of the original investigation, the children's varied perceptions of specific tasks influenced their performance in important ways. Limitations were noted in a strictly quantitative analysis of the experimental data. Ethnographic techniques were applied to a post-hoc examination of the children's responses. The reflective and qualitative nature of ethnography was used to account for these different perceptions and their impact on the children's behavior.
Discourse Markers in Adult-Controlled Therapy: Implications for Child Centered Intervention
Authors: Kovarsky Dana
Published: December 2008

Broadly considered, ethnographers of communication are interested in cultural descriptions of patterned uses of language and speech in groups, institutions, communities, or societies (Sherzer, 1977: 44-5). For ethnographers of cammunication, the speech event has been the major methodological unit of analysis (Baugh and Sherzer, 1984). Speech events are activities characterized by rules or norms for the use of speech and language (Hymes, 1972: 56). These activities are recognized by community members as "distinct wholes, separate from other types of discourse" (Gumperz 1972: 17), and may occur within specific temporal and spatial boundaries (Labov and Fanshel, 1977). As part of a larger investigation which examined child language therapy lessons as speech events (Kovarsky, 1989a), an analysis of certain discourse markers illuminated dimensions of adult-centered therapy to be considered in child-oriented intervention approaches.
Ethnographic Interviewing: Asking the Right Questions To the Right People in the Right Ways
Authors: Westby Carol E.
Published: December 2008

Current philosophy in early childhood education advocates family-centered intervention goals for handicapped children. To develop appropriate gaals for children from diverse cultures, professionals must understand parents' beliefs and values regarding the family's and child's resources and needs; and they must adopt an ecological framework that considers children's functioning within the broader aspects of their environment. Interviewing provides a means of obtaining the information necessary to develop culturally appropriate, family-centered intervention goals. This paper describes the influence of culture on the interview process and describes an approach to ethnographic interviewing of families of handicapped children that enables professionals to ask the right questions to the right people in the right ways so they can assist families in meeting the needs of their children.
Teaching Expressive Writing to Hearing-Impaired Students
Authors: Luckner John L. , Isaacson Stephen L.
Published: December 2008

Many hearing-impaired students have great difficulty communicating effectively and sharing ideas using written language. The traditional approach of assigning writing correcting the errors, returning the paper, and expecting improvement is still widely practiced today. In contrast, this paper presents a model for teaching written language to hearing-impaired students that emphasizes a high degree of student involvement, with specific attention given to planning revising and rewriting as well as transcribing. Recommendations also are made regarding direct instruction in necessary writing skills.
Social and Nonsocial Decentration in Hearing-Impaired and Normal Hearing Children
Authors: Cates David S. , Shontz Franklin C.
Published: December 2008

Tweny-three hearing-impaired and 25 normally hearing children between 7 and 14 years of age were administered a social decentration task, a nonsocial decentration task (a set of conservation problems), and a test of nonverbal intelligence. Although the two groups did not differ with respect to nonverbal intelligence, the hearing-impaired children obtained significantlv lower scores than their normally hearing peers on both the social and nonsocial decentration measures. Within both groups, there was a significant positive correlation between social decentration and nonsocial decentration, which is consistent with Piaget's contention that centration-decentration is a cognitive dimension underlying the structuring of both social and nonsocial content. Within the hearing-impaired sample, degree of hearing loss was not associated with either social or nonsocial decentration.
Language Samples From Visually Impaired Four and Five-Year Olds
Authors: Erin Jane N.
Published: December 2008

This paper presents an analysis of language samples from 12 children, including 4 blind, 4 sighted, and 4 children with low vision. The samples were generated as the children examined a set of household objects and talked about them with the investigator. Analysis of the samples focused on four areas: syntactic structures, pronoun usage, sentence types, and topic/content. With respect to syntactic structures, the mean length of utterance (ML U) and number of syntactic incongruities were examined. These indicated slightly greater complexity of utterances by the sighted group as compared to both visually impaired groups. Blind and low vision children also demonstrated a higher frequency of inappropriate pronoun use than the sighted group. Visually impaired students also used less variation in sentence types, employing a high frequency of repetitive forms, including questions. Finally, there were fewer instances of experiential narrative and imaginative play in the samples obtained from the visually impaired children. The samples suggested that a greater variation in the level of language maturity existed in the samples from these children. Related literature suggests that the altered environment of the visually impaired child may influence this outcome.
An Investigation of the Oral Narratives of Normal and Language-Learning Disabled Children
Authors: Klecan-Aker Joan S. , Kelty Kimberly R.
Published: December 2008

The purpose of this study was to assess the developmental levels of the stories of normal and language-learning disabled children. Findings revealed that the normal subjects told more complex stories. The results are discussed relative to the assessment and treatment of school-age children with language-learning deficits.
Therapeutic Strategies for Language Disordered Children: The Impact of Visual Imagery on Verbal Encoding in Vocabulary Instruction
Authors: Clark Joan , Klegan-Aker Joan S.
Published: December 2008

This investigation focused on the impact of visual imagery on the strategies of categorization and verbal rehearsal in group vocabulary instruction among language disordered children. Sixteen sixth and seventh grade language disordered students were divided into two groups. These groups were taught twenty target vocabulary items through instruction revolving around the verbal encoding strategies of categorization and verbal rehearsal. One group was taught the words using an approach which emphasized visual imagery; the other did not receive this type of emphasis. Results of this investigation indicate that visual imagery may enhance verbal encoding strategies in vocabulary instruction among language disordered children. Implications of the results are discussed.
Impact of a Program to Facilitate Mother-Infant Communication in High-Risk Families of High-Risk Infants
Authors: Haney Michele , Klein M. Diane
Published: December 2008

This article presents follow-up results of the Mother-Infant Communication Project (MICP), a program designed to facilitate caregivers' uses of communicative interaction strategies with their infants labeled high-risk. Three groups of mother-infant dyads were included in the study: a group receiving home visits only, a group receiving home visits plus a group experience, and a comparison group. Results showed MICP mothers overall were significantly better than comparison group mothers on the Home Observation for Measurement of the Environment (HOME) Scale. In addition, children of MICP mothers who received a group experience in addition to home visits performed significantly better on the Receptive-Expressive Emergent Language (REEL) Scale at 18 months than both the home visits only group and the comparison group. Implications of the findings for intervention efforts are discussed.
Profiling Communication and Symbolic Abilities in Young Children
Authors: Wetherby Amy M. , Prizant Barry M.
Published: December 2008

This article briefly addresses the potential detrimental impact of early language and communication impairments on a child's emotional and behavioral development, later educational achievement, and on the family's well-being. It focuses on children who fall along a continuum from a specific language delay to a more pervasive social-communicative impairment. Assessment is discussed from the perspective of profiling a young child's communication and symbolic abilities. Strategies for sampling communication and symbolic abilities in young children who are not yet talking or who are at early language stages are described. Emphasis is placed on involving the caregiver as an active participant interacting with the child, as an informant about the child's competence, and as a collaborator in consensus-building and decision-making based on shared observations and perceptions. The contribution of profiling to the early identification of a language impairment as well as to the design of an early intervention program is discussed and illustrated with two clinical vignettes.
Team Talk: Communication Skills for Early Intervention Teams
Authors: Briggs Margaret H.
Published: December 2008

With a background on effective team functioning serving as a conceptual framework, information on ways early intervention team members can improve their communication is provided. Qualities of effective teams and the roles members assume on teams is discussed. This article presents a step-by-step process for creating a transdisciplinary team. Specific information of interest to early intervention professionals on the necessary skills for successful communicative interaction is offered and behaviors that serve as barriers to team communication are outlined.
Effects of Multisensory Speech Training and Visual Phonics on Speech Production of a Hearing-Impaired Child
Authors: Zaccagnini Cindy M. , Antia Shirin D.
Published: December 2008

A single subject alternating treatments design was used to examine the effects of intensive multisensory speech training with and without the use of Visual Phonics hand cues on the speech production of a profoundly hearing-impaired child. Six target phonemes were trained, three using only multisensory techniques and three using multisensory techniques and Visual Phonics. Daily evaluations of the subject's speech production indicated that all targets showed improvement. The addition of Visual Phonics to multisensory training did not result in speech production gains. All targets were generalized to new words and maintained after the intervention was discontinued.
Redefining Assessment as a Holistic Discovery Process
Authors: Gillam Ron , McFadden Teresa U.
Published: December 2008

Holistic assessment provides SLPs and other educators with information about the processes that are at work when students with special language and learning needs function successfully and unsuccessfully in contexts that require interpersonal and cognitive/academic communication. SLPs and other educators can build portfolios that present holistic pictures of students' abilities in a variety of learning contexts. This paper presents three practical strategies (reading miscue analysis, holistic scoring of written stories, and dynamic assessment)for collecting, organizing, and interpreting language data that can be incorporated into a larger portfolio assessment.
Let's Pretend! A Semantic Analysis of Preschool Children's Play
Authors: Marvin Chris , Hunt-Berg Mary
Published: December 2008

This study explored the semantic content of children's talk during their pretend play at home and at preschool. The spontaneous speech of ten children (C.A. 4:0 to 5:2)was tape-recorded during two hours of preschool activity and two hours following dismissal from school. Transcripts were coded for references to pretend/fantasy time, and references to specific persons and content were noted. There were no significant differences in the frequency with which children used referents to pretend/fantasy time at home and preschool. During their pretend play, the children spoke most often about themselves alone or themselves with others in both settings. Significantly more references were made to family members at home; peers and self were referenced significantly more often during pretend play at school. The actions and locations of themselves or others were frequent referents in both settings. Fantasy/cartoon characters were used by half of the children in each setting but were not used significantly more in one setting or another. Familiar daily routines were common play themes at home and at school, but never were associated with the activity of cartoon/fantasy characters. The results are discussed as they relate to the design and implementation of intervention programs for children with speech-language impairments in integrated settings with nondisabled peers.
Discourse-Based Language Intervention
Authors: Skarakis-Doyle Elizabeth , Murphy Lisa
Published: December 2008

It was the purpose of this study to examine the effect of supplementing the pragmatically-based procedure of focused stimulation with structured opportunities for verbal practice using vertical constructions. This procedure was employed to facilitate the use of the modal verbs “should” and “must” and their communicative function of obligation as treatment targets. An equal phase interaction additive single subject experimental design was employed to address this question with the presence or absence of a vertical construction component being experimentally manipulated. Results indicated that focused stimulation was an effective treatment procedure and the additional component of a vertical construction enhanced that effectiveness.
Effects of Collaboration on Language Performance
Authors: Bland Lauren E. , Prelock Patricia A.
Published: December 2008

Language samples from fourteen students with communication disorders were obtained over a three year period to determine the effectiveness of a language-in-the-classroom (LIC)intervention model. While there were few differences noted in syntax, semantics or morphology for students served in a collaborative model as compared to students served in a pull-out model, significant differences in the completeness and intelligibility of student utterances were noted. Results indicated that students who received intervention using an LIC model had more complete/intelligible utterances and fewer incomplete/unintelligible utterances than students who received intervention using a more traditional pull-out model. Implications for speech-language pathologists (SLPs)are provided.
The Effects of Focused Stimulation for Promoting Vocabulary in Young Children with Delays
Authors: Girolametto Luigi , Pearce Patsy Steig , Weitzman Elaine
Published: December 2008

The interactive model of language intervention optimizes parent-child interaction patterns by training parents to increase their responsiveness to the child's focus and interests, and provide language models appropriate to the child's level and plan-of-the-moment. We explored the effects of a focused stimulation version of this intervention approach, in which parents used interactive intervention techniques, but targeted specific vocabulary. In this pilot study, 16 mothers and their preschool-aged children with language delays were randomly assigned to treatment and delayed-treatment (control)groups. Vocabulary targets were individually selected for each child based on the child's phonetic repertoire and parent report of vocabulary development. In accord with program objectives, children in the treatment group used more target words and acquired more symbolic play gestures than children in the control group. No significant differences were found between the two groups at posttest for control words, or for a general measure of vocabulary development. Finally, mothers of children in the experimental group reported a reduction in aggressive/destructive behaviors in their children after intervention.
Language Assessment Methods For Three Age Groups of Children
Authors: Beck Ann R.
Published: December 2008

This article describes results of a survey of licensed, midwestern, school-based speech-language pathologists regarding methods used to assess the language of children ages 3 to 5 years, 6 to 11 years, and 12 to 18 years. Striking similarities were found in methods used for each age group. Results of this survey are also compared to those of a similar survey done in a western state to indicate if national tendencies in language assessment may be present. How these methods relate to assessment practices recommended in literature and reasons cited by respondents for choosing these methods are discussed.
Maybe the Problem Isn't Whole Language
Authors: Norris Janet
Published: December 2008

Whole Language has come under recent attack, especially as some programs implementing instruction considered “whole language” have seen decreases in achievement scores in reading and writing (Fry, 1995). This has led many educators and parents to question whole language as a teaching philosophy and to mandate the structured, systematic teaching of phonics and other skill-based methods. However, many problems that are attributed to whole language as a philosophy are the outcomes of other educational dynamics that have led to ineffective practices. Issues related to identification of methodologies as “whole language,” failure to provide adequate training or mentoring to teachers, confusion of language as a communication process with language arts skills, the professional reluctance to provide teachers with a scaffold as an entry level into whole language, and failure to apply known principles of intervention within a whole language framework for children with special needs have all clouded the question regarding the efficacy of whole language philosophy and practice. Examination of these issues may clarify some of the present controversy, and provide considerations for program evaluation and change.
Career Pathways for Related Service Paratherapists Working in Early Intervention and Other Education Settings
Authors: Longhurst Thomas M.
Published: December 2008

This article presents issues in personnel training practices for paraprofessionals providing related services in early intervention and education settings. The generic term paratherapist is used to refer to persons who work under the supervision of professional level therapists in physical therapy, occupational therapy, and speech-language pathology. A philosophy of related service paratherapist utilization is presented and discussed. Current and future needs for paratherapists are summarized. A description of career pathways for paratherapists from high school to advanced graduate studies is described and advantages of well developed career pathways for participants in career planning are discussed.
A Case Study of a Speech-Language Pathologist's Supervision of Assistants in a School Setting
Authors: French Nancy K.
Published: December 2008

The purpose of this article is to present a single case study about a newly graduated speech-language pathologist working in a small, urban school district and her experiences with a series of speech-language assistants having various levels of qualification and personality types. The case illustrates how levels of professional supervision skills, pre-service paraprofessional training, professional/paraprofessional role distinctions, hiring practices, pay, and working conditions interact and impact on the successful use of speech-language paraprofessionals working in education settings. Evidence gathered in the case support the contention that pre-service preparation for speech-language pathologists to function in supervisory roles is an important factor in ensuring the appropriate use of speech-language paraprofessionals.
Necessity
Authors: Haas Eileen M.
Published: December 2008

Although publically funded educational environments have endeavored to provide support services, including speech-language pathology, to comply with the mandates of P.L. 94–142, guaranteeing a free and appropriate education to all children has been extremely difficult for many educational settings. The necessity of providing an appropriate education to all children in American educational settings has caused some educational managers such as I “invent” flexible systems of service delivery that include speech-language paraprofessionals to overcome specific problems such as the lack of knowledgeable or qualified personnel. As a mother of a 12-year-old medically fragile child, I have found speech-language paraprofessionals an invaluable asset to my daughter's educational program. It is my opinion that a practical, common sense, hands-on approach for delivering support services to learners in need of communication intervention includes the utilization of speech-language paraprofessionals.
The Ability of Children with Specific Language Impairment to Participate in a Group Decision Task
Authors: Fujiki Martin , Brinton Bonnie , Robinson Lee A. , Watson Valyne J.
Published: December 2008

This study examined the ability of 6 children with specific language impairment (SLI), ages 8:10 to 12:5 (years; months), to participate in a group negotiation task. Each child interacted with two peers to select toys that children their age would enjoy. Performance was compared to both chronological age-similar (CS)peers and language similar (LS)peers performing the same task. Analyses of the resulting interactions indicated that subjects with SLI produced significantly fewer utterances than the other children in the triad. Similar differences were not observed in the CS or LS triads. Additionally, significantly fewer utterances were addressed to the children with SLI than to the other children in their triad. CS and LS triads produced much more balanced interactions, with differences in the number of utterances addressed to each child failing to reach significance.
What is required for transition from the ESL classroom to the general education classroom? A case study of two classrooms
Authors: Brice Alejandro , Perkins Carol
Published: December 2008

Speech-language pathologists in the schools and classroom teachers repeatedly face the challenge of how best to provide services and instruction for students who are learning English as a second language (ESL). A better understanding of second language acquisition issues, such as code-switched and code-mixed behaviors, is essential because, as Aguirre (1989) maintains, code switching is obvious and unavoidable with bilingual students. An ethnographic observational study of ESL and regular classroom discourse was performed. The researchers asked the questions: "What language skills must the bilingual student possess to succeed in the general education classroom, and what skills should the SLP be aware of in assessing bilingual students?" This study found that bilingual students in the general education classroom needed to shift and adapt their language uses to meet the demands of the classroom. The general education classroom proceeded at a fast pace of instruction, which necessitated fast processing abilities and more independent student follow-through. Learning is dependent upon precise understanding of long teacher utterances, many utterances spoken within a short time period with few opportunities for clarification or seeking of help. The student in the ESL classroom who is also enrolled in the general education classroom is using three language systems : listening and speaking Spanish, English, and a mixed series of Spanish and English code-switched and code-mixed language. Code-switching and code-mixing serves as a bridge between Spanish and English and is not an indicator of a language disorder or language confusion. It is typically used by the teachers, aides, and the students. The findings of this study suggest that language evaluations should incorporate ethnographic observations to obtain a truer picture of what occurs, where it occurs, how it occurs, why it occurs, and how often it occurs. Hence, use of dynamic assessment procedures and ethnographic observations may help make apparent the distinction between a language disorder and typical difficulties associated with second language acquisition.
A Comparison of the Peer Social Behavior of Children Who are Deaf/Hard of Hearing and Hearing
Authors: Antia Shirin D. , Dittillo Deborah A.
Published: December 2008

This study examined the peer social behaviors of 38 children who were deaf or hard of hearing (D/HH) and 44 hearing children during free play in small integrated groups. Nine minutes of free play data were videotaped for each child and analyzed for the presence of 15 social behaviors in four categories: peer interaction; play; peer initiations/child responses; child initiations/peer responses. Children who were D/HH and hearing engaged equally frequently in positive and negative interaction, parallel play, and solitary play. Both groups engaged in similar patterns of initiations and responses with peers. However, children who were D/HH engaged in less linguistic interaction and associative/cooperative play than the hearing children.
Children's Language Proficiency at Ages 2 and 3 as Predictors of Behavior Problems, Social and Cognitive Development at Age 3
Authors: Carson David K. , Klee Thomas , Lee Sarah , Williams Karen C. , Perry Cecyle K.
Published: December 2008

This study examined the relationship between language proficiency, behavior problems, and other areas of development in a sample of 36 children ranging from 36–40 months (M = 37.3; SD = 1.1). Although none of the children were in the clinical range of behavioral disturbance, the findings indicated a strong general association between deficiencies in both expressive and receptive language and children's behavioral difficulties. Specifically, deficits in expressive language at age 2 (M = 25.5 mo.; SD = 0.6 mo.) were more predictive of internalizing rather than externalizing behavior problems at age 3, including symptoms associated with anxiety and depression, withdrawal, sleep and somatic problems. However, deficits in receptive language at age 3 were more predictive of these same types of symptoms at age 3, along with more destructive kinds of behaviors. Scores on measures of receptive language abilities at age 2 were positively predictive of social and cognitive development at age 3. These findings indicate a need for early identification of language delays in young children to help prevent deficits in language that might be linked to behavior problems or delays in other areas of development. Further, our results suggest the need for early intervention, especially for children who display both language delays and behavioral difficulties.
Listener Judgments of Impaired Narration at Two Age Levels
Authors: Boulet David , Bliss Lynn S. , Bryce Shelly , Linebaugh Catherine
Published: December 2008

Listener judgments of the narrative coherence of children with specific language impairment (SLI) were compared with their peers with normal language development (NL) at two age levels. Two groups of listeners (lay and professionals) rated audiotapes of the children's narrative discourse. The ratings for the children with SLI improved over time. The younger children with SLI had lower ratings than the children with NL. Differences between the groups for the older children were not as evident. Judgments differed slightly depending upon the background of the raters. Clinical implications of the data are discussed.
Ethnography
Authors: Hendryx-Bedalov Patricia M.
Published: December 2008

As the diversity and complexity of children with special needs continues to increase in the United States so does the need for culturally sensitive assessment and intervention for communication disorders among these children. Ethnographic methods are augmenting traditional normatively based standardized assessments and behavioral prescriptive intervention. This article provides a basic introduction to the ethnographic method, while giving suggestions for its use as a clinical tool to study culture, context and communication from a client-centered perspective.
Botulinum Toxin-A in Children With Congenital Spastic Hemiplegia Does Not Improve Upper Extremity Motor-Related Function Over Rehabilitation Alone: A Randomized Controlled Trial
Authors: Rameckers E.A.A. , Speth L.A.W.M. , Duysens J. , Vles J.S.H. , Smits-Engelsman B.C.M.
Published: December 2008

Background. Rehabilitation of the upper extremity in children with hemiplegic cerebral palsy has not been compared to the same intensity of therapy combined with injected botulinum toxin (BTX). Objective. To measure the short-term (2 weeks) and long-term (6 and 9 months) effects of a standardized functional training program versus without the addition of chemodenervation of forearm and hand muscles. Methods. Twenty children with spastic hemiplegia, aged 4 to 16 years, were matched for baseline characteristics and then randomized to standardized functional physical and occupational therapies for 6 months (PT/OT group) or to the same therapies plus multimuscle BTX-A (BTX+ group). Main outcome measures were isometric generated force, overshoot and undershoot (force production error), active and passive range of motion by goniometry (ROM), stretch restricted angle (SRA) of joints, Ashworth scores at the elbow and wrist, and the Melbourne assessment of unilateral upper limb function. All measures were performed at baseline, 2 weeks after BTX-A, 6 months (end of therapy), and then 3 months after termination of the therapy. Results. Clinical measures (muscle tone, active ROM of wrist and elbow) showed improvement in both groups. However, no significant differences emerged between groups on functional measures. Generated force decreased directly after the BTX-A injection but increased during the therapy period. The PT/OT group, however, showed a significantly higher increase in force and accuracy with therapy compared with the BTX+ therapy group. Conclusions. Functional rehabilitation therapies for the upper extremity increase manual isometric flexor force at the wrist and ROM, but BTX injections cause weakness and do not lead to better outcomes than therapy alone.
Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations
Authors: Akagi Tadayuki , Shih Lee-Yung , Kato Motohiro , Kawamata Norihiko , Yamamoto Go , Sanada Masashi , Okamoto Ryoko , Miller Carl W. , Liang Der-Cherng , Ogawa Seishi , Koeffler H. Phillip
Published: December 2008

Acute promyelocytic leukemia (APL) is a hematopoietic malignant disease characterized by the chromosomal translocation t(15;17), resulting in the formation of the PML-RARA gene. Here, 47 t(15;17) APL samples were analyzed with high-density single-nucleotide polymorphism microarray (50-K and 250-K SNP-chips) using the new algorithm AsCNAR (allele-specific copy-number analysis using anonymous references). Copy-number-neutral loss of heterozygosity (CNN-LOH) was identified at chromosomes 10q (3 cases), 11p (3 cases), and 19q (1 case). Twenty-eight samples (60%) did not have an obvious alteration (normal-copy-number [NC] group). Nineteen samples (40%) showed either one or more genomic abnormalities: 8 samples (17%) had trisomy 8 either with or without an additional duplication, deletion, or CNN-LOH (+8 group); and 11 samples (23%) had genomic abnormalities without trisomy 8 (other abnormalities group). These chromosomal abnormalities were acquired somatic mutations. Interestingly, FLT3-ITD mutations (11/47 cases) occurred only in the group with no genomic alteration (NC group). Taken together, these results suggest that the pathway of development of APL differs in each group: FLT3-ITD, trisomy 8, and other genomic changes. Here, we showed for the first time hidden abnormalities and novel disease-related genomic changes in t(15;17) APL.
Transplantation of allogeneic T cells alters iron homeostasis in NOD/SCID mice
Authors: Bair Steven , Spaulding Emily , Parkkinen Jaakko , Shulman Howard M. , Lesnikov Vladimir , Beauchamp Mary , Canonne-Hergaux François , Kowdley Kris V. , Deeg H. Joachim
Published: December 2008

Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT), but the mechanisms leading to overload are unknown. Here, we determined iron levels and the expression of iron regulatory proteins in the liver and gut of nonobese diabetic–severe combined immunodeficient (NOD/SCID) mice that underwent transplantation with syngeneic (histocompatible) or allogeneic (histoincompatible) T lymphocytes. Infusion of histoincompatible T cells resulted in a significant rise in serum iron levels and liver iron content. Iron deposition was accompanied by hepatocyte injury and intestinal villous damage. Feeding of low- or high-iron diet was associated with appropriate ferroportin 1 and hepcidin responses in mice given histocompatible T cells, whereas mice given histoincompatible T cells showed inappropriate up-regulation of duodenal ferroportin 1 and a loss of expression of hepatic hepcidin. These findings suggest that alloreactive T cell–dependent signals induced dysregulation of intestinal iron absorption, which contributed to liver iron overload after HCT.
Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control
Authors: Ferre April L. , Hunt Peter W. , Critchfield J. William , Young Delandy H. , Morris Megan M. , Garcia Juan C. , Pollard Richard B. , Yee Hal F. , Martin Jeffrey N. , Deeks Steven G. , Shacklett Barbara L.
Published: December 2008

There exists a unique group of persons who are able to durably control HIV in the absence of therapy. The mechanisms of control in these persons remain poorly defined. In this study, we examined CD8+ T-cell responses in blood and rectal mucosa from 17 “elite controllers” (viral load < 75 copies/mL), 11 “viremic controllers” (75-2000 copies/mL), 14 noncontrollers (> 10 000 copies/mL), and 10 antiretroviral-treated persons (< 75 copies/mL). Production of interferon-γ, interleukin-2, tumor necrosis factor-α, macrophage inflammatory protein-1β, and CD107a by CD8+ T cells in response to HIV-1 Gag stimulation was measured using flow cytometry. Our hypothesis was that “polyfunctional” T cells producing multiple antiviral factors would be most abundant in mucosal tissues of HIV controllers. Mucosal CD8+ T-cell responses were significantly stronger and more complex in controllers than in antiretroviral-suppressed persons (P = .0004). The frequency of 4-function responses in rectal mucosa was higher in controllers than in noncontrollers and patients on therapy (P < .0001). Mucosal responses in controllers were frequently stronger and more complex than blood responses. These findings demonstrate that many controllers mount strong, complex HIV-specific T-cell responses in rectal mucosa. These responses may play an important role in mucosal immune surveillance, as suggested by their relative enrichment among persons who control HIV in the absence of therapy.
NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study
Authors: Asnafi Vahid , Buzyn Agnès , Le Noir Sandrine , Baleydier Frédéric , Simon Arnauld , Beldjord Kheira , Reman Oumedaly , Witz Francis , Fagot Thierry , Tavernier Emmanuelle , Turlure Pascal , Leguay Thibaut , Huguet Françoise , Vernant Jean-Paul , Daniel Francis , Béné Marie-Christine , Ifrah Norbert , Thomas Xavier , Dombret Hervé , Macintyre Elizabeth
Published: December 2008

Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials. In 88 cases (62%) there were demonstrated NOTCH1 mutations (42% heterodimerization [HD], 10% HD+proline glutamate serine threonine [PEST], 6% PEST, 2% juxtamembrane mutations, 2% transactivation domain [TAD]) and 34 cases (24%) had FBXW7 mutations (21 cases had both NOTCH1 and FBXW7 mutations); 40 cases (28%) were wild type for both. There was no significant correlation between NOTCH1 and/or FBXW7 mutations and clinico-biologic features. Median event-free survival (EFS) and overall survival (OS) were 36 versus 17 months (P = .01) and not reached versus 32 months (P = .004) in patients with NOTCH1 and/or FBXW7 mutations versus other patients, respectively. Multivariate analysis showed that the presence of NOTCH1/FBXW7 mutations was an independent good prognostic factor for EFS and OS (P = .02 and P = .01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7 mutation identifies a large group of patients with a favorable outcome that could justify individual therapeutic stratification for T-ALL.
Subcellular localization of ammonium transporters in Dictyostelium discoideum
Authors: Kirsten Janet H , Xiong Yanhua , Davis Carter T , Singleton Charles K
Published: December 2008

Background

With the exception of vertebrates, most organisms have plasma membrane associated ammonium transporters which primarily serve to import a source of nitrogen for nutritional purposes. Dictyostelium discoideum has three ammonium transporters, Amts A, B and C. Our present work used fluorescent fusion proteins to determine the cellular localization of the Amts and tested the hypothesis that the transporters mediate removal of ammonia generated endogenously from the elevated protein catabolism common to many protists.

Results

Using RFP and YFP fusion constructs driven by the actin 15 promoter, we found that the three ammonium transporters were localized on the plasma membrane and on the membranes of subcellular organelles. AmtA and AmtB were localized on the membranes of endolysosomes and phagosomes, with AmtB further localized on the membranes of contractile vacuoles. AmtC also was localized on subcellular organelles when it was stabilized by coexpression with either the AmtA or AmtB fusion transporter. The three ammonium transporters exported ammonia linearly with regard to time during the first 18 hours of the developmental program as revealed by reduced export in the null strains. The fluorescently tagged transporters rescued export when expressed in the null strains, and thus they were functional transporters.

Conclusion

Unlike ammonium transporters in most organisms, which import NH3/NH4
+ as a nitrogen source, those of Dictyostelium export ammonia/ammonium as a waste product from extensive catabolism of exogenously derived and endogenous proteins. Localization on proteolytic organelles and on the neutral contractile vacuole suggests that Dictyostelium ammonium transporters may have unique subcellular functions and play a role in the maintenance of intracellular ammonium distribution. A lack of correlation between the null strain phenotypes and ammonia excretion properties of the ammonium transporters suggests that it is not the excretion function that is important for coupling ammonia levels to the slug versus culmination choice, but rather a sensor and/or signaling function of these proteins that is important.
A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan
Authors: Lin Chien-Hsing , Li Ling-Hui , Ho Sheng-Feng , Chuang Tzu-Po , Wu Jer-Yuarn , Chen Yuan-Tsong , Fann Cathy SJ
Published: December 2008

Background

Copy number variations (CNVs) have recently been recognized as important structural variations in the human genome. CNVs can affect gene expression and thus may contribute to phenotypic differences. The copy number inferring tool (CNIT) is an effective hidden Markov model-based algorithm for estimating allele-specific copy number and predicting chromosomal alterations from single nucleotide polymorphism microarrays. The CNIT algorithm, which was constructed using data from 270 HapMap multi-ethnic individuals, was applied to identify CNVs from 300 unrelated Han Chinese individuals in Taiwan.

Results

Using stringent selection criteria, 230 regions with variable copy numbers were identified in the Han Chinese population; 133 (57.83%) had been reported previously, 64 displayed greater than 1% CNV allele frequency. The average size of the CNV regions was 322 kb (ranging from 1.48 kb to 5.68 Mb) and covered a total of 2.47% of the human genome. A total of 196 of the CNV regions were simple deletions and 27 were simple amplifications. There were 449 genes and 5 microRNAs within these CNV regions; some of these genes are known to be associated with diseases.

Conclusion

The identified CNVs are characteristic of the Han Chinese population and should be considered when genetic studies are conducted. The CNV distribution in the human genome is still poorly characterized, and there is much diversity among different ethnic populations.
Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages
Authors: Calura Enrica , Cagnin Stefano , Raffaello Anna , Laveder Paolo , Lanfranchi Gerolamo , Romualdi Chiara
Published: December 2008

Background

Skeletal muscle mass can be markedly reduced through a process called atrophy, as a consequence of many diseases or critical physiological and environmental situations. Atrophy is characterised by loss of contractile proteins and reduction of fiber volume. Although in the last decade the molecular aspects underlying muscle atrophy have received increased attention, the fine mechanisms controlling muscle degeneration are still incomplete. In this study we applied meta-analysis on gene expression signatures pertaining to different types of muscle atrophy for the identification of novel key regulatory signals implicated in these degenerative processes.

Results

We found a general down-regulation of genes involved in energy production and carbohydrate metabolism and up-regulation of genes for protein degradation and catabolism. Six functional pathways occupy central positions in the molecular network obtained by the integration of atrophy transcriptome and molecular interaction data. They are TGF-β pathway, apoptosis, membrane trafficking/cytoskeleton organization, NFKB pathways, inflammation and reorganization of the extracellular matrix. Protein degradation pathway is evident only in the network specific for muscle short-term response to atrophy. TGF-β pathway plays a central role with proteins SMAD3/4, MYC, MAX and CDKN1A in the general network, and JUN, MYC, GNB2L1/RACK1 in the short-term muscle response network.

Conclusion

Our study offers a general overview of the molecular pathways and cellular processes regulating the establishment and maintenance of atrophic state in skeletal muscle, showing also how the different pathways are interconnected. This analysis identifies novel key factors that could be further investigated as potential targets for the development of therapeutic treatments. We suggest that the transcription factors SMAD3/4, GNB2L1/RACK1, MYC, MAX and JUN, whose functions have been extensively studied in tumours but only marginally in muscle, appear instead to play important roles in regulating muscle response to atrophy.
Forced IFIT-2 expression represses LPS induced TNF-alpha expression at posttranscriptional levels
Authors: Berchtold Susanne , Manncke Birgit , Klenk Juliane , Geisel Julia , Autenrieth Ingo B , Bohn Erwin
Published: December 2008

Background

Interferon induced tetratricopeptide repeat protein 2 (IFIT-2, P54) belongs to the type I interferon response genes and is highly induced after stimulation with LPS. The biological function of this protein is so far unclear. Previous studies indicated that IFIT-2 binds to the initiation factor subunit eIF-3c, affects translation initiation and inhibits protein synthesis. The aim of the study was to further characterize the function of IFIT-2.

Results

Stimulation of RAW264.7 macrophages with LPS or IFN-γ leads to the expression of IFIT-2 in a type I interferon dependent manner. By using stably transfected RAW264.7 macrophages overexpressing IFIT-2 we found that IFIT-2 inhibits selectively LPS induced expression of TNF-α, IL-6, and MIP-2 but not of IFIT-1 or EGR-1. In IFIT-2 overexpressing cells TNF-α mRNA expression was lower after LPS stimulation due to reduced mRNA stability. Further experiments suggest that characteristics of the 3'UTR of transcripts discriminate whether IFIT-2 has a strong impact on protein expression or not.

Conclusion

Our data suggest that IFIT-2 may affect selectively LPS induced protein expression probably by regulation at different posttranscriptional levels.