bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development of Social Anxiety in Adolescents With Autism Spectrum Disorders
Authors: Bellini Scott
Published: June 2008

The present study examined factors contributing to the development of social anxiety in adolescents with autism spectrum disorders (ASD). In particular, the study examined the contribution of social skill deficits and physiological hyperarousal to the development of social anxiety in individuals with ASD. Forty-one adolescents with high-functioning ASD participated in the study. The results of a multiple regression analysis suggest that the proposed model (i.e., the combination of social skills and physiological arousal) is a significant predictor of social anxiety in this sample. A developmental pathways model is proposed that identifies potential predisposing or protective factors that may contribute to the development, protection, or remediation of social anxiety in adolescents with autism.
Increasing Physical Activity in Individuals With Autism
Authors: Todd Teri , Reid Greg
Published: June 2008

This study investigated the outcomes of an intervention package on participation in tWo physical activities: snoWshoeing and Walking/jogging. Three male secondary school students Who had been diagnosed With autism and Were attending a school for students With intellectual disabilities participated in a 6-month outdoor physical activity program. The authors used a changing conditions design; the program Was divided into six phases by the amount of edible reinforcers provided during sessions. A self-monitoring board, verbal cuing, and edible reinforcers Were used in the study. Distance snoWshoed, Walked, and jogged per 30-min session increased as edible and verbal reinforcement decreased. The results suggest that interventions can be developed to promote sustained participation in physical activity for individuals With autism.
Parent Perspectives on Role Engagement
Authors: Stoner Julia B. , Angell Maureen E.
Published: June 2008

This exploratory study employed qualitative methodology to analyze intervieW data that emerged from face-to-face intervieWs With eight parents of four children With autism spectrum disorder. The study focused on the roles these parents played as they monitored their children's educational programs and interacted With school professionals. The findings revealed that parent participants, especially mothers, consistently engaged in four roles: (a) negotiator, (b) monitor, (c) supporter, and (d) advocate. In addition, the degree of perceived parental trust in education professionals affected the extent of their engagement in the roles of negotiator, monitor, and supporter. The data also indicated that parents' education monitoring Was mediated by the trust the parents placed on the education professionals. The authors discuss the implications of the findings for the improvement of parent—professional interactions and offer recommendations for future research.
Increasing Appropriate Social Interactions of Children With Autism Spectrum Disorders Using Social Stories™
Authors: Scattone Dorothy , Tingstrom Daniel H. , Wilczynski Susan M.
Published: June 2008

To date there are more than one dozen studies that validate the use of Social Stories™ as an effective behavioral intervention. Many of these studies focused on decreasing inappropriate behaviors (e.g., aggression, screaming, and grabbing toys), and most combined Social Stories With another intervention. The present study used a multiple baseline design across participants to investigate the effectiveness of Social Stories When used as a sole intervention to increase the appropriate social interactions of 3 children With autism spectrum disorders toWard peers both With and Without disabilities. During baseline, participants demonstrated feW appropriate social interactions, although all had some functional expressive language. An increase in appropriate social interactions occurred for 2 of the participants after the intervention Was implemented. These findings suggest that Social Stories may be effective for some children With autism spectrum disorders; hoWever, the population they best serve has not yet been fully identified.
Assessing Behavioral Flexibility in Individuals With Developmental Disabilities
Authors: Green Vanessa A. , Sigafoos Jeff , Pituch Keenan A. , Itchon Jonathan , O'Reilly Mark , Lancioni Giulio E.
Published: June 2008

Researchers associate an insistence on sameness or lack of behavioral flexibility With autism and Asperger syndrome, but feW studies have sought to identify specific situations in Which individuals insist on sameness. Along these lines, We developed the Behavioral Flexibility Rating Scale (BFRS) and conducted an Internet survey of parents of individuals With autism, Asperger syndrome, and DoWn syndrome. A total of 726 respondents submitted usable returns during the 3-month survey period. Parent report indicated that individuals With Asperger syndrome shoWed the most problems in relation to the insistence on sameness as measured by the BFRS, folloWed by individuals With autism and DoWn syndrome, respectively. When diagnosis Was controlled, there Were no gender or age differences. This preliminary investigation suggests that the BFRS may be useful in identifying specific situations associated With an insistence on sameness. Identifying specific situations in Which individuals insist on sameness or shoW a lack of behavioral flexibility may be useful in planning interventions focused on promoting greater behavioral flexibility.
Author Productivity and Publication Trends in Autism-Specific Journals From 1997 to 2004
Authors: de la Cruz Berenice , Cannella-Malone Helen I. , Edrisinha Chaturi , Sigafoos Jeff , Robinson Dan , Son Seung-Hyun
Published: June 2008

The 20 most productive authors (in terms of number of articles authored) Were identified across three major autism-specific journals (Autism: An International Journal of Research and Practice, Focus on Autism and Other Developmental Disabilities, and the Journal of Autism and Developmental Disorders) published betWeen 1997 and 2004. Of the top 20 authors, 11 Worked outside the United States, and 9 Were Women. Most articles included several coauthors, suggesting that most authors Were involved in collaborative Work. Most of the published research Was assessment research, and slightly less than half Was funded. Limitations of this study and future research are discussed.
The Application of PECS in a Deaf Child With Autism
Authors: Malandraki Georgia A. , Okalidou Areti
Published: June 2008

A 10-year-old nonverbal Greek boy, C.Z., Who had been diagnosed With both bilateral sensorineural profound hearing loss and autism, Was taught to use the Picture Exchange Communication System (PECS), With some modifications and extensions, over a 4-month intensive intervention period. C.Z.'s original communication and behavioral status as Well as the PECS application process are presented, along With the communicative, language, and psychosocial outcomes folloWing the intervention program. FolloW-up data Were collected 6 months post.
Incorporating Interests and Structure to Improve Participation of a Child With Autism in a Standardized Assessment
Authors: Vacca John J.
Published: June 2008

The rise in the number of children With autism poses challenges to professionals in the field of early care and education. The restricted patterns of communicating, relating, and behaving seen often in children With autism necessitate a sophisticated approach to assessment. There is an increasing need in the field to use alternative assessment approaches in order to alloW professionals to interact and communicate With the child on multiple levels. Assessment approaches that provide the child With choices yield data that go beyond confirmation of a diagnosis to include information about suitable educational and therapeutic interventions and programming outcomes as Well as ideas to support functioning in the natural environment. This article describes an innovative approach to assessing a girl With autism. The approach includes incorporating interests and a structured schedule.
Using a Self-as-Model Video Combined With Social Stories™ to Help a Child With Asperger Syndrome Understand Emotions
Authors: Bernad-Ripoll Susana
Published: June 2008

Using an AB design With generalization, this study sought to determine the effectiveness of presenting videotaped emotions and Social Stories™ to teach a 9-year-old child With Asperger syndrome to recognize and understand emotions in himself and to generalize them to other situations in his home. Data collected in the child's home shoWed an improvement betWeen baseline and intervention in the child's ability to recognize emotions and understand their occurrence.
Outcomes of a Social and Vocational Skills Support Group for Adolescents and Young Adults on the Autism Spectrum
Authors: Hillier Ashleigh , Fish Tom , Cloppert Patricia , Beversdorf David Q.
Published: June 2008

Adolescents and young adults With autism spectrum disorders (ASD) frequently experience social isolation and vocational failure. Although social skills groups are vital, relatively feW model programs have been developed for this age group. This article revieWs the model and evaluation of the Aspirations program, an 8-Week social and vocational skills support group for adolescents and young adults With ASD. Self-report measures, including appraisal of peer relations and empathy, Were completed pre- and post-Aspirations. Data from structured observations Were also examined for changes in frequency of contributions made by group members over the course of the program. In addition, notes taken during staff meetings and feedback sessions With group members, and separately With their parents, Were revieWed for further evidence of the program's success. The results from these measures support the efficacy of the Aspirations program and provide insight into implementing a successful model for this population.
The Impact of Social—Behavioral Learning Strategy Training on the Social Interaction Skills of Four Students With Asperger Syndrome
Authors: Bock Marjorie A.
Published: June 2008

This study examined the effect of a social—behavioral learning strategy intervention (SODA) on the social interaction skills of 4 elementary school children With Asperger syndrome (AS). More specifically, the study investigated the effect of SODA training on the abilities of 4 children With AS to participate in cooperative learning activities, play organized sport games, and visit With their peers during lunch. A multiple-baseline-across-settings design (TaWney & Gast, 1984) Was used to analyze social behavior Without SODA (baseline) and With SODA (intervention) during fourth- or fifth-grade social studies cooperative learning activities, noon recess, and lunch. Maintenance probes occurred once a month for 5 months folloWing completion of the intervention. The participants benefited from the SODA intervention. They presented increased percentages of time spent learning cooperatively, playing organized sport games, and visiting during lunch When SODA training began. When SODA training discontinued, they maintained high performance across all study conditions, nearly matching those achieved by 4 peers Without disabilities. In addition, the participants presented long-term memory of SODA 1 month after maintenance.
Measurement of Social Communication Skills of Children With Autism Spectrum Disorders During Interactions With Typical Peers
Authors: Murdock Linda C. , Cost Hollie C. , Tieso Carol
Published: June 2008

The Social-Communication Assessment Tool (S-CAT) Was created as a direct observation instrument to quantify specific social and communication deficits of children With autism spectrum disorders (ASD) Within educational settings. In this pilot study, the instrument's content validity and interrater reliability Were investigated to determine the degree to Which the S-CAT categorically discriminated betWeen children With ASD and those Without ASD. S-CAT ratings of 16 children With ASD Were compared to the ratings of 16 children Without ASD using a one-factor analysis of variance (ANOVA). Differences in verbal initiations, verbal responses, joint attention, and total interactions Were significant at the .01 level. Differences in nonverbal communication attempts Were not significant. The results suggest that the S-CAT is valid for discriminating betWeen children With and Without ASD.
Use of Strategy Instruction to Improve the Story Writing Skills of a Student With Asperger Syndrome
Authors: Delano Monica E.
Published: June 2008

More empirical studies are needed that evaluate interventions to improve the academic functioning of students with Asperger syndrome (AS). The purpose of this exploratory study was to evaluate the use of Self-Regulated Strategy Development (SRSD) writing instruction (Graham, Harris, MacArthur, & Schwartz, 1991) with an adolescent with AS. A multiple baseline design across three responses was used to assess the effects of SRSD instruction. Strategy instruction sequentially targeted the student's use of action words, describing words, and revisions. Following instruction, the student demonstrated gains in both the quantity and quality of his writing samples.
Reading Comprehension Instruction for Students With Autism Spectrum Disorders
Authors: Chiang Hsu-Min , Lin Yueh-Hsien
Published: June 2008

The authors reviewed studies on teaching reading comprehension to students with autism spectrum disorders (ASD) with a focus on text (academic reading) comprehension and sight word (functional) comprehension. Eleven of 754 studies met the inclusion criteria: participants with ASD, published in English in a peer-reviewed journal, and use of an experimental design. Participants, setting, academic or functional reading comprehension, and instructional methods across studies were summarized and examined. Instructional methods employed were compared to those identified by the National Reading Panel as effective for students without disabilities. Suggestions for future research and practice are discussed.
Leadership and Self-Determination
Authors: Johnson John R.
Published: June 2008

This article briefly reviews attributes and elements identified in the literature for promoting the self-determination and self-advocacy of people with disabilities. In addition, to identify which elements of self-determination and self-advocacy are discussed as elements of effective leadership, a small portion of the general leadership literature is also reviewed. Of specific interest is determining which self-determination practices that have emerged in the literature devoted to people with disabilities also appear in the general leadership literature as essential, generic leadership practices. Conceptual distinctions are drawn among the notions of self-determination, self-advocacy, empowerment, and leadership. A number of conclusions are drawn and are supported by the review, suggesting that (a) self-determination and self-advocacy are essential to effective leadership based on the frequency with which attributes of self-determination are identified as elements of effective leadership; (b) leadership involves skills, competencies, and strategies that focus on collective action to achieve common goals, whereas self-determination and self-advocacy typically focus on individual action directed toward personal goals; and (c) effective leadership is fundamentally an exercise in collective self-determination. Recommendations to increase the focus and attention to the leadership development of people with developmental disabilities are suggested.
Developing Skills and Concepts for Self-Determination in Young Adults with Autism
Authors: Fullerton Ann , Coyne Phyllis
Published: June 2008

The impact of a program to develop knowledge and skills for self-determination in young adults with autism is examined through students' in-class contributions and through pre-post interviews with students and parents. Program components included knowledge about autism, communication skills, life planning, and goal setting. Visual organization and social information were key instructional strategies used to facilitate student understanding and participation. Students initiated more discussion and use of a number of skills and concepts after the program in other settings. These instances in which the participants applied the concepts and strategies taught are analyzed. The challenges students faced in understanding and applying concepts related to self-determination are also examined. Directions for further program and instructional strategy development are discussed.
A Functional Model of Self-Determination
Authors: Wehmeyer Michael L.
Published: June 2008

This article describes a functional model of self-determination as a dispositional characteristic of individuals. This model has been used to conduct research to examine the impact of self-determination on the lives of people with developmental and other disabilities, to describe the development of self-determination, and to design interventions to promote self-determination for people with and without disabilities.
Auditory Integration Training
Authors: Edelson Stephen M. , Arin Deborah , Bauman Margaret , Lukas Scott E. , Rudy Jane H. , Sholar Michelle , Rimland Bernard
Published: June 2008

Auditory problems are common in individuals with autism. Several previous studies have indicated that Auditory Integration Training (AIT), a sound-based intervention, may bring about significant improvement in autism. AIT entails listening to specially processed music for a total of 10 hours over a 10- to 20-day period. In the present study, 19 individuals with autism were assigned at random to either an experimental group (n = 9), who listened to AIT-processed music, or a placebo group (n = 10), who listened to the same but unprocessed music. All evaluators were blind to group assignment. Behavioral, electrophysiological (ERP), and audiometric measures were assessed prior to and following AIT. A significant decrease in Aberrant Behavior Checklist scores was observed in the experimental group at the 3-month follow-up assessment. Of the 19 participants, only three experimental group members and two placebo group members were able to perform the auditory P300 ERP task. All five participants showed abnormal P300 ERPs prior to the AIT listening sessions. Three months following AIT, all three treated participants showed a dramatic improvement in their auditory P300 ERP, whereas none of the participants in the placebo group showed change. The participants' poor language and attention skills precluded collecting sufficient data for formal statistical evaluation of the results from the battery of audiometric tests.
A Multimedia Social Story Intervention
Authors: Hagiwara Taku , Smith Myles Brenda
Published: June 2008

Although social stories have been used as a positive support intervention for people with autism and other developmental disabilities, their utility has primarily been supported by anecdotal records. This study developed an intervention that used social stories in a computer-based format. The results revealed that overall the social story intervention using a multimedia social story program for three boys with autism was effective.
Respite Care Needs of Parents of Children with Developmental Disabilities
Authors: Abelson A. Geoffrey
Published: June 2008

The purpose of this study was to identify the respite care needs, and the impact of a lack of respite care, among families of children with developmental disabilities. A respite care needs assessment survey was completed by 574 lowan families of children with developmental disabilities. The results documented a void in the availability and accessibility of respite services regardless of demography, income level, or extent of disability. Respondents generally perceived that the availability of respite care services would improve overall family functioning.
Strabismus in Autism Spectrum Disorder
Authors: Kaplan Melvin , Rimland Bernard , Edelson Stephen M.
Published: June 2008

Strabismus ("crossed eyes") has been reported to be markedly elevated in individuals with autism. This article presents the findings from two studies of strabismus in autism. A clinical optometric examination of 34 individuals with autism, ages 7 to 19 years, found a strabismus rate of 50% (65% with exotropia and 35% with esotropia). A parent survey of 7,640 families found a reported incidence of 20% (18% in boys, 29% in girls). As strabismus occurs in only 2% to 4% of the general population, both studies reported here confirm the high rate of strabismus in autism. A number of concomitants of strabismus, derived from questionnaire data, are reported.
School Intervention for Inclusion of Students With and Without Disabilities
Authors: Cooper Mark J. , Griffith Kimberly G. , Filer Janet
Published: June 2008

A common understanding shared by parents and educators of students with disabilities is the students' tremendous need in the area of socialization. Having and maintaining friendships is an integral part of children's development. Often, students are ill prepared for the inclusion of schoolmates with and without disabilities. Consequently, a comprehensive school intervention model designed for the effective inclusion of all students should be planned. The purpose of this article is to share successful practices for the socialization of students with and without disabilities in the general education classroom. A model of inclusion conducive to establishing positive interactions and communication among students with and without disabilities is presented. Intervention strategies involving the relationship between two elementary school students and their schoolmates are used to demonstrate the effectiveness of the intervention.
Self-Determination for People with Developmental Disabilities and Autism
Authors: Ward Michael J. , Meyer Roger N.
Published: June 2008

Self-determination has been identified with people with disabilities only since 1988. This article traces the history of the civil rights, disability rights, and self-advocacy movements. What began as a small federal initiative is presently a national effort in health care and other disability service systems and embraces ideas such as self-direction and consumer control. The road to self-determination has been different for three distinct populations: people with physical disabilities, people with cognitive disabilities, and people with Asperger syndrome and other autistic conditions. However, they all are striving to control their own lives and gain respect in their communities. Future self-determination efforts must further leadership skills and accentuate the positive values of having a disability.
The Development of Communicative Functions and Means in Students with Autism
Authors: Calloway Carie J. , Myles Brenda Smith , Earles Theresa L.
Published: June 2008

The purpose of this study was to analyze the acquisition of communicative functions and means in 15 children and youth with autism over a 1-year period. Study participants made advances in skills development in both functions and means, replacing more primitive forms of communication with more advanced forms. Functions appeared to follow a developmental sequence from behavior regulation to social interaction to joint attention.
Examining the Services Received by Young Children with Autism and Their Families
Authors: Kohler Frank W.
Published: June 2008

This study was designed to examine the services received by 3- to 9-year-old children with autism and pervasive developmental disabilities. Four questions were addressed: (1) What services are received? (2) How are families involved in their services? (3) How do providers ensure that their services have continuity or are organized around a common set of child needs? and (4) What problems do families report? These questions were addressed by conducting a telephone interview with 25 families in western Pennsylvania. Results indicated that families interacted with a host of different agencies and professionals. Several problems also became apparent, as many families reported difficulty accessing needed services and minimal involvement in planning or implementing these interventions.
Use of Evidence-Based Practice As a Method for Evaluating the Effects of Secretin on a Child with Autism
Authors: Richman David M. , Reese R. Matthew , Daniels Debora
Published: June 2008

Standardized assessment instruments and direct observation data were collected pre-and postadministration (2 weeks after administration) on the effects of secretin on a 4-year-old boy diagnosed with autism. Information was collected on the three major diagnostic categories associated with autism: communication deficiencies, repetitive behavior and interests, and impaired social interactions. No changes in communication functioning, occurrences of stereotypic behavior, or social interaction were observed 2 weeks after administration of secretin. A 3-month follow-up interview with the child's primary care provider supported empirical data suggesting no substantial behavioral changes after the secretin administration. Results are discussed in terms of controversial treatments for children with autism and related developmental disorders.
Sorting Laundry
Authors: Bock Marjorie A.
Published: June 2008

The current study replicates and extends learning strategy research investigating the effects of categorization strategy training on the abilities of children with autism to accurately complete uni-, bi-, and tridimensional sorting tasks. This study extends prior research by (a) using authentic sorting activities for categorization strategy training, (b) using both low- and high-functioning children with autism, and (c) assessing categorization strategy generalization across multiple settings and teachers using untrained sorting items. Five children with autism (i.e., two low- and three high-functioning) showed strategy acquisition and generalization during training. Four children (i.e., one low- and three high-functioning) showed strategy maintenance 4 months later. The other child showed uni- and bidimensional strategy maintenance 4 months later; however, tridimensional strategy maintenance was unconfirmed. Thus results from the current study substantiate the worth of categorization strategy training for five children with autism.
Implementing a Multimethod, Multilevel Literacy Program for Students with Mental Retardation
Authors: Hedrick Wanda B. , Katims David S. , Carr Norma J.
Published: June 2008

The present descriptive study was a year-long investigation into the literacy development of nine elementary students with mild to moderate mental retardation (mean CA = 9.8; IQ scores available for seven students, mean IQ = 57.7; IQ range = 40-76). The teacher instructed the students using a balanced, multimethod, multilevel language arts framework that blended more traditional approaches to teaching reading, such as phonics and basal instruction, with holistic and contextualized approaches that included reading children's literature and process writing. The children made measurable gains in several areas, including the use of word identification and reading comprehension strategies, metalinguistics, written language, and confidence with the written word. The authors suggest practical applications for classroom teachers.
Successful engagement in an early literacy intervention
Authors: Scull Janet A. , Lo Bianco Joseph
Published: June 2008

The aim of the research reported here was to investigate why a percentage of students experience continued difficulty in literacy learning while participating in Reading Recovery. It was hypothesized that this is to do with particular aspects of teacher—learner interactions. Accordingly the study used ethnographic methodology to describe teacher—learner interactions generally and to then examine selected dimensions of the interaction between particular cohorts of students and their teachers. Specifically investigated were the characteristics of this group, mapping students' learning trajectory, and identifying key points and events that impact on teacher decision-making processes with regard to student learning. The learners who participated in this study were 10 children identified as being at risk of literacy failure. Their participation in one-to-one literacy support resulted in six of the children making considerable progress, with the other four identified as requiring ongoing support beyond the short-term intervention provided by Reading Recovery. The reasons for the successful outcome for the six learners are related to the ways that their teachers orchestrated positive reading and writing opportunities through closely focused verbal support. While this `helping talk' appeared to be decisive in the six successful cases, it was productive but inadequate in the remaining four.
Negotiation of `how to' at the cross-section of cultural capital and habitus: Young children's procedural practices in a student-led literacy group
Authors: Christ Tanya , Wang X. Christine
Published: June 2008

In order to become productive members of an academic community, it is important for students to master its procedural practices. By adapting Bourdieu's concepts of cultural capital, habitus, and field, we examined procedural practices of first-graders from minority and low-socioeconomic-status backgrounds in the context of student-led literacy groups in an urban classroom. We applied a variety of qualitative methods to collect, analyze, and triangulate the data in this ethnographic study. The results showed that differences in cultural capital and habitus intersected within the group context and affected procedural practices in three ways: deciding to accept or reject procedural practices, scaffolding other students' use of classroom-based procedural practices, and co-constructing procedural practices. The findings indicate that grasping procedural practice knowledge and norms influences students' ability to effectively participate in classroom literacy activities, and building students' cultural capital concerning procedural practices enhances their ability to engage in these practices.
Mother—child shared reading with print and digital texts
Authors: Ji Eun Kim  , Anderson Jim
Published: June 2008

The purpose of this study was to (1) compare mother—child interactions in three contexts: shared reading with a book in a traditional print format, with an electronic book in a CD-ROM format, and with an electronic book in a video clip format; (2) compare mother—child interactions with a three-year-old and a seven-year-old; and (3) compare children's extra-textual talk during the shared readings. Results indicated mother—child interactions differed in the contexts, with more complex talk evident in the electronic texts. There were differences in mother—child interactions with the two children that seemed contingent on the child's age and experiences. Finally, children's extra-textual talk differed depending on their ages, and these seemed to be context specific.
Targeting MEK/MAPK signal transduction module potentiates ATO-induced apoptosis in multiple myeloma cells through multiple signaling pathways
Authors: Lunghi Paolo , Giuliani Nicola , Mazzera Laura , Lombardi Guerino , Ricca Micaela , Corradi Attilio , Cantoni Anna Maria , Salvatore Luigi , Riccioni Roberta , Costanzo Antonio , Testa Ugo , Levrero Massimo , Rizzoli Vittorio , Bonati Antonio
Published: June 2008

We demonstrate that blockade of the MEK/ERK signaling module, using the small-molecule inhibitors PD184352 or PD325901 (PD), strikingly enhances arsenic trioxide (ATO)–induced cytotoxicity in human myeloma cell lines (HMCLs) and in tumor cells from patients with multiple myeloma (MM) through a caspase-dependent mechanism. In HMCLs retaining a functional p53, PD treatment greatly enhances the ATO-induced p53 accumulation and p73, a p53 paralog, cooperates with p53 in caspase activation and apoptosis induction. In HMCLs carrying a nonfunctional p53, cotreatment with PD strikingly elevates the (DR4 + DR5)/(DcR1 + DcR2) tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) receptors ratio and caspase-8 activation of ATO-treated cells. In MM cells, irrespective of p53 status, the combined PD/ATO treatment increases the level of the proapoptotic protein Bim (PD-mediated) and decreases antiapoptotic protein Mcl-1 (ATO-mediated). Moreover, Bim physically interacts with both DR4 and DR5 TRAIL receptors in PD/ATO-treated cells, and loss of Bim interferes with the activation of both extrinsic and intrinsic apoptotic pathways in response to PD/ATO. Finally, PD/ATO treatment induces tumor regression, prolongs survival, and is well tolerated in vivo in a human plasmacytoma xenograft model. These preclinical studies provide the framework for testing PD325901 and ATO combination therapy in clinical trials aimed to improve patient outcome in MM.
A review of transfusion practice before, during, and after hematopoietic progenitor cell transplantation
Authors: Gajewski James L. , Johnson Viviana V. , Sandler S. Gerald , Sayegh Antoine , Klumpp Thomas R.
Published: June 2008

The increased use of hematopoietic progenitor cell (HPC) transplantation has implications and consequences for transfusion services: not only in hospitals where HPC transplantations are performed, but also in hospitals that do not perform HPC transplantations but manage patients before or after transplantation. Candidates for HPC transplantation have specific and specialized transfusion requirements before, during, and after transplantation that are necessary to avert the adverse consequences of alloimmunization to human leukocyte antigens, immunohematologic consequences of ABO-mismatched transplantations, or immunosuppression. Decisions concerning blood transfusions during any of these times may compromise the outcome of an otherwise successful transplantation. Years after an HPC transplantation, and even during clinical remission, recipients may continue to be immunosuppressed and may have critically important, special transfusion requirements. Without a thorough understanding of these special requirements, provision of compatible blood components may be delayed and often urgent transfusion needs prohibit appropriate consultation with the patient's transplantation specialist. To optimize the relevance of issues and communication between clinical hematologists, transplantation physicians, and transfusion medicine physicians, the data and opinions presented in this review are organized by sequence of patient presentation, namely, before, during, and after transplantation.
Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1
Authors: Ahmad Rasheed , El Bassam Souad , Cordeiro Paulo , Menezes José
Published: June 2008

Exposure of human monocytic cells to herpes simplex virus type 1 (HSV-1) results in immediate up-regulation of interleukin (IL)–15 gene expression. However, the receptor involved in this induction is not known. Here, we provide evidence that this induction depends on TLR2-mediated signaling pathway. Through the use of small interfering RNAs (siRNAs), we demonstrate that HSV-1–induced up-regulation of IL-15 gene expression in monocytic THP1 cells requires the presence of the adaptors MyD88, IRAK1, and TRAF6. Interestingly, TIRAP/Mal, an adaptor molecule specifically recruited to TLR2 and TLR4, was also required for maximal up-regulation of IL-15. This response was completely abrogated by anti-TLR2, but not anti-TLR4, blocking mAbs in both primary monocytes and THP1 cells. Furthermore, THP1 cells rendered defective in TLR2 expression by disrupting the expression of Sp1, a major transcription factor involved in TLR2 promoter activity, were unable to up-regulate IL-15 gene expression in response to HSV-1. In addition, HSV-1–induced NF-κB activation was significantly reduced after neutralization of TLR2 and the adaptor proteins. Altogether, these results unequivocally show that HSV-1 induces TLR2-dependent activation of IL-15 gene expression, which requires the recruitment of both MyD88 and TIRAP/Mal and the activation of IRAK1 and TRAF6 leading to NF-κB translocation to the nucleus.
MHC class I–specific inhibitory receptors and their ligands structure diverse human NK-cell repertoires toward a balance of missing self-response
Authors: Yawata Makoto , Yawata Nobuyo , Draghi Monia , Partheniou Fotini , Little Ann-Margaret , Parham Peter
Published: June 2008

Variegated expression of 6 inhibitory HLA class I–specific receptors on primary NK cells was studied using high-dimension flow cytometry in 58 humans to understand the structure and function of NK-cell repertoires. Sixty-four subsets expressing all possible receptor com-binations were present in each repertoire, and the frequency of receptor-null cells varied among the donors. Enhancement in missing-self response between NK subsets varied substantially where subset responses were defined by donor KIR/HLA allotypes, reflecting the differences in interaction between inhibitory receptors and their ligands. This contrasted to the enhancement conferred by NKG2A, which was constant and of intermediate strength. We infer a mechanism that modulates frequencies of the NK subsets displaying diverse levels of missing-self response, a system that reduces the presence of KIR-expressing subsets that display either too strong or too weak a response and effectively replaces them with NKG2A-expressing cells in the repertoire. Through this high-resolution analysis of inhibitory receptor expression, 5 types of NK-cell repertoire were defined by their content of NKG2A+/NKG2A− cells, frequency of receptor-null cells, and degree of KIR receptor coexpression. The analyses provide new perspective on how personalized human NK-cell repertoires are structured.
Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation
Authors: Beers Stephen A. , Chan Claude H. T. , James Sonya , French Ruth R. , Attfield Kathrine E. , Brennan Claire M. , Ahuja Anupama , Shlomchik Mark J. , Cragg Mark S. , Glennie Martin J.
Published: June 2008

Anti-CD20 monoclonal antibodies (mAbs) are classified into type I (rituximab-like) or type II (tositumomab-like) based on their ability to redistribute CD20 molecules in the plasma membrane and activate various effector functions. To compare type I and II mAbs directly in vivo and maximize Fc effector function, we selected and engineered mAbs with the same mouse IgG2a isotype and assessed their B-cell depleting activity in human CD20 transgenic mice. Despite being the same isotype, having similar affinity, opsonizing activity for phagocytosis, and in vivo half-life, the type II mAb tositumomab (B1) provided substantially longer depletion of B cells from the peripheral blood compared with the type I mAb rituximab (Rit m2a), and 1F5. This difference was also evident within the secondary lymphoid organs, in particular, the spleen. Failure to engage complement did not explain the efficacy of the type II reagents because type I mAbs mutated in the Fc domain (K322A) to prevent C1q binding still did not display equivalent efficacy. These results give support for the use of type II CD20 mAbs in human B-cell diseases.
Isolation of bacteria-containing phagosomes by magnetic selection
Authors: Lönnbro Per , Nordenfelt Pontus , Tapper Hans
Published: June 2008

Background

There is a growing awareness of the importance of intracellular events in determining the outcome of infectious disease. To improve the understanding of such events, like phagosome maturation, we set out to develop a versatile technique for phagosome isolation that is rapid and widely applicable to different pathogens.

Results

We developed two different protocols to isolate phagosomes containing dead or live bacteria modified with small magnetic particles, in conjunction with a synchronized phagocytosis protocol and nitrogen cavitation. For dead bacteria, we performed analysis of the phagosome samples by microscopy and immunoblot, and demonstrated the appearance of maturation markers on isolated phagosomes.

Conclusion

We have presented detailed protocols for phagosome isolation, which can be adapted for use with different cell types and prey. The versatility and simplicity of the approach allow better control of phagosome isolation, the parameters of which are critical in studies of host-bacteria interaction and phagosome maturation.
Dumpy-30 family members as determinants of male fertility and interaction partners of metal-responsive transcription factor 1 (MTF-1) in Drosophila
Authors: Vardanyan Alla , Atanesyan Lilit , Egli Dieter , Raja Sunil Jayaramaiah , Steinmann-Zwicky Monica , Renkawitz-Pohl Renate , Georgiev Oleg , Schaffner Walter
Published: June 2008

Background

Metal-responsive transcription factor 1 (MTF-1), which binds to metal response elements (MREs), plays a central role in transition metal detoxification and homeostasis. A Drosophila interactome analysis revealed two candidate dMTF-1 interactors, both of which are related to the small regulatory protein Dumpy-30 (Dpy-30) of the worm C. elegans. Dpy-30 is the founding member of a protein family involved in chromatin modifications, notably histone methylation. Mutants affect mating type in yeast and male mating in C. elegans.

Results

Constitutive expression of the stronger interactor, Dpy-30L1 (CG6444), in transgenic flies inhibits MTF-1 activity and results in elevated sensitivity to Cd(II) and Zn(II), an effect that could be rescued by co-overexpression of dMTF-1. Electrophoretic mobility shift assays (EMSA) suggest that Dpy-30L1 interferes with the binding of MTF-1 to its cognate MRE binding site. Dpy-30L1 is expressed in the larval brain, gonads, imaginal discs, salivary glands and in the brain, testes, ovaries and salivary glands of adult flies. Expression of the second interactor, Dpy-30L2 (CG11591), is restricted to larval male gonads, and to the testes of adult males. Consistent with these findings, dpy-30-like transcripts are also prominently expressed in mouse testes. Targeted gene disruption by homologous recombination revealed that dpy-30L1 knockout flies are viable and show no overt disruption of metal homeostasis. In contrast, the knockout of the male-specific dpy-30L2 gene results in male sterility, as does the double knockout of dpy-30L1 and dpy-30L2. A closer inspection showed that Dpy-30L2 is expressed in elongated spermatids but not in early or mature sperm. Mutant sperm had impaired motility and failed to accumulate in sperm storage organs of females.

Conclusion

Our studies help to elucidate the physiological roles of the Dumpy-30 proteins, which are conserved from yeast to humans and typically act in concert with other nuclear proteins to modify chromatin structure and gene expression. The results from these studies reveal an inhibitory effect of Dpy-30L1 on MTF-1 and an essential role for Dpy-30L2 in male fertility.
Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD)
Authors: Yoneda Masato , Hotta Kikuko , Nozaki Yuichi , Endo Hiroki , Uchiyama Takashi , Mawatari Hironori , Iida Hiroshi , Kato Shingo , Hosono Kunihiro , Fujita Koji , Yoneda Kyoko , Takahashi Hirokazu , Kirikoshi Hiroyuki , Kobayashi Noritoshi , Inamori Masahiko , Abe Yasunobu , Kubota Kensuke , Saito Satoru , Maeyama Shiro , Wada Koichiro , Nakajima Atsushi
Published: June 2008

Background

Genetic factors as well as environmental factors are important in the development of NAFLD and in this study we investigated associations between polymorphisms of peroxisome proliferators-activated receptor γ coactivator 1α polymorphism (PPARGC1A) and NAFLD.

Aims

We recruited 115 patients with biopsy-proven NAFLD, 65 with NASH and 50 with simple steatosis, and 441 healthy control subjects and investigated 15 SNPs ofPPARGC1A.

Results

SNP rs2290602 had the lowestpvalue in the dominant mode (p= 0.00095), and the odds ratio for NAFLD (95% CI) was 2.73 (1.48 – 5.06). rs2290602 was significantly associated with NAFLD even when the most conservative Bonferroni's correction was applied (p= 0.0143). The frequency of the T allele of rs2290602 was significantly higher in the NASH patients than in the control subjects (p= 0.00093, allele frequency mode), and its frequency in the NASH patients tended to be higher than in the simple steatosis patients (p= 0.09). The results of the real-time RT-PCR study showed that intrahepatic mRNA expression ofPPARGC1Awas lower in the TT group than in the GG or GT group at SNP rs2290602 (p = 0.0454).

Conclusion

This is the first study to demonstrate a significant association between genetic variations inPPARGC1Aand NAFLD. This finding suggested thatPPARGC1Apolymorphism and lower expression ofPPARGC1AmRNA in the liver are an important genetic contribution to etiology of NAFLD.
Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis
Authors: Tran Bich NH , Nguyen Nguyen D , Eisman John A , Nguyen Tuan V
Published: June 2008

Background

The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in BMD in high bone mass pedigrees. Subsequent population-based studies of the association between the LRP5 gene and BMD have yielded conflicting results. The present study was aimed at examining the association between LRP5 gene and BMD by using meta-analysis.

Methods

A systematic electronic search of literature was conducted to identify all published studies in English on the association between LRP5 gene and osteoporosis-related phenotypes, including bone mineral density and fracture. BMD data were summarized from individual studies by LRP5 genotype, and a synthesis of data was performed with random-effects meta-analyses. After excluding studies on animal and review papers, there were 19 studies for the synthesis. Among these studies, 10 studies used the rs3736228 (A1330V) polymorphism and reported BMD values.

Results

The 10 eligible studies comprised 16,705 individuals, with the majority being women (n = 8444), aged between 18 – 81 years. The overall distribution of genotype frequencies was: AA, 68%, AV and VV, 32%. However, the genotype frequency varied significantly within as well as between ethnic populations. On random-effects meta-analysis, lumbar spine BMD among individuals with the AA genotype was on average 0.018 (95% confidence interval [CI]: 0.012 to 0.023) g/cm2 higher than those with either AV or VV genotype. Similarly, femoral neck BMD among carriers of the AA genotype was 0.011 (95%CI: 0.004 to 0.017) g/cm2 higher than those without the genotype. While there was no significant heterogeneity in the association between the A1330V polymorphism and lumbar spine BMD (p = 0.55), the association was heterogeneous for femoral neck BMD (p = 0.05). The probability that the difference is greater than one standard deviation was 0.34 for femoral neck BMD and 0.54 for lumbar spine BMD.

Conclusion

These results suggest that there is a modest effect of the A1330V polymorphism on BMD in the general population, and that the modest association may limit its clinical use.