Involvement of a phospholipase D in the mechanism of action of granulocyte-macrophage colony-stimulating factor (GM-CSF): priming of human neutrophils in vitro with GM-CSF is associated with accumulation of phosphatidic acid and diradylglycerol.

The generation of diradylglycerol (DRG) and phosphatidic acid (PdtOH) was investigated in neutrophils primed with granulocyte-macrophage colony-stimulating factor (GM-CSF). Mass accumulation of DRG and PdtOH was measured using reversed-phase high performance liquid chromatography and thin layer chromatography, respectively. GM-CSF had no direct effect on the levels of PdtOH and DRG, but it increased PdtOH generation and the late phase of DRG accumulation in human neutrophils stimulated with FMLP. The elevation of the mass of PdtOH peaked approximately 100 s and clearly preceded that of DRG, which peaked at 150 s. The diacylglycerol kinase inhibitor R59022 enhanced the sustained increase in DRG but did not produce a parallel inhibition in PdtOH production. GM-CSF was without effect on the level of inositol 1,4,5-triphosphate [Ins(1,4,5)P3] and did not affect the liberation of Ins(1,4,5)P3 induced by FMLP. These findings exclude the involvement of the PtdIns(4,5)P2-specific phospholipase C/diacylglycerol pathway in the sustained phase of DRG accumulation. The early (30-s) appearance of PdtOH clearly suggests that GM-CSF enhanced FMLP receptor-linked phospholipase D (PLD) generation of PdtOH. PLD was assessed more directly by formation of labeled phosphatidylethanol (PEt) through PLD capacity of catalyzing a trans-phosphatidylation in presence of ethanol. The formation of PEt associated with a concomitant decrease in PdtOH directly demonstrated that the mechanism by which GM-CSF enhances PdtOH production is activation of a PLD active on phosphatidylcholine. This study provides evidence that the mechanism of action of GM-CSF involves upregulation of PLD activity leading to enhanced generation of PdtOH and DRG in FMLP-stimulated neutrophils. These findings may provide the basis for several of the priming effects of GM-CSF.

FMRI activation in language areas correlates with verb generation performance in children.

Functional MRI mapping of language areas in children frequently employs a covert verb generation task. Because responses are not monitored, the relationship between fMRI activation and task performance is unknown. We compared fMRI activation during covert and overt verb generation to performance during the overt task. 15 children, ages 11-13 years, listened to concrete nouns and responded with related verbs covertly and overtly. A clustered fMRI acquisition allowed for recording of overt responses without motion artifacts. Region of interest analysis was also performed in areas that exhibited correlation between activation and performance during overt verb generation in left inferior frontal and left superior temporal gyri (along with their right hemisphere homologues). Regression analysis determined that during both covert and overt generation, left hemisphere regions showed positive correlations with average counts of verbs generated during the overt task. These results suggest that increased verb generation performance leads to increased activation. In addition, overt performance may be used as an estimator of covert performance.

Unwanted sexual contact on campus: a comparison of women's and men's experiences.

While sexual victimization continues to be a problem on college campuses, recent attention has been drawn to understanding gender differences in victimization rates and consequences. To date, these studies remain relatively few in number. The current study surveyed 651 male and female undergraduate students about unwanted sexual experiences during 1 academic year. Comparison of men and women revealed expected differences in incidence rates, with women reporting higher rates of unwanted contact. Within the subsample of reported victims, however, there was gender similarity in terms of the context of unwanted sexual experiences. Analyses also revealed the negative consequences of these experiences for both men and women and low rates of disclosure regardless of gender. Across the full sample of students surveyed, there were interesting gender differences in knowledge of campus support services, with women more likely to have attended a prevention program and to have indicated greater knowledge of rape crisis services.

Electrophysiological dissociation between verbal and nonverbal semantic processing in learning disabled adults.

Event-related potentials (ERPs) were recorded as 16 adults with learning disabilities (LD) and 16 controls were presented with two sets of stimuli. The first set comprised pairs of line drawings and environmental sounds (nonverbal condition); the second consisted of printed and spoken words (verbal condition). In the controls, semantically related items elicited smaller N400s than unrelated items in both conditions, with opposing hemispheric asymmetries for spoken words and environmental sounds. The LD group did not show a significant difference between related and unrelated words, despite a robust context effect for nonspeech sounds. The results suggest anomalous processing limited to the verbal domain in a simple semantic association task in the LD group. Semantic deficits in this group may reflect a relatively specific deficit in forming verbal associations rather than a more general difficulty that spans both verbal and nonverbal domains.

Image manipulation and error estimation for MRI analysis.

Manipulation of MRI images prior to volumetric analysis is a common practice that may unwittingly lead to errors in measurement. In this study, we examine the effects of two types of image manipulation: changes in the total number of slices used to obtain volume estimates (slice sampling rate) and image rotation. A phantom containing two regularly-shaped and two irregularly-shaped regions of interest (ROIs) was scanned using an SPGR sequence and 1-mm slices. Changes in slice sampling rate produced marked effects on volume estimation of irregularly-shaped ROls. Comparatively little error was associated with changes in slice sampling rates for regularly-shaped ROIs. In addition, there was an interaction between image rotation in non-orthogonal planes and slice sampling rate. The data suggests that the ability to detect anatomical effects may be influenced by an investigator's choices concerning the number of slices included in a region of interest and image rotation when estimating volumes.

Time course of word identification and semantic integration in spoken language.

The minimum duration signal necessary to identify a set of spoken words was established by the gating technique; most words could be identified before their acoustic offset. Gated words were used as congruous and incongruous sentence completions, and isolation points established in the gating experiment were compared with the time course of semantic integration evident in event-related brain potentials. Differential N400 responses to contextually appropriate and inappropriate words were observed about 200 ms before the isolation point. Semantic processing was evident before the acoustic signal was sufficient to identify the words uniquely. Results indicate that semantic integration can begin to operate with only partial, incomplete information about word identity. Influences of semantic constraint, word frequency, and rate of presentation are described.

Sources of error in the quantitative analysis of MRI scans.

The increasing use of quantitative analysis of MRI scans in the literature has produced a need to identify potential sources of bias in such analysis procedures. Six sources of bias are demonstrated in this paper. These include bias attributable to partial volume effects, head tilt, plane of view, use of noncontiguous slices, contrast/intensity manipulations, and magnetic inhomogeneities. The magnitude of bias for each source varied according to whether a hemisphere or regions within a hemisphere were measured, with regional effects typically exceeding hemisphere effects.

The distinct HERG missense mutation L564P causes long QT syndrome in one French Canadian family.

BACKGROUND: Long QT syndrome is a congenital abnormality of cardiac repolarization causing syncope and sudden death from ventricular tachyarrhythmias known as torsades de pointes. This hereditary cardiac disorder often shows an increase of the value of the QT interval corrected for heart rate over 0.45 s in a 12-lead electrocardiogram. OBJECTIVE: To find and identify pertinent mutations occurring in French Canadians by extracting genomic DNA from blood samples and performing a combination of polymerase chain reaction (PCR), single-strand conformational polymorphism and DNA sequencing. RESULTS: A novel mutation was identified in the S5 region of the HERG potassium channel. In codon 564 CTA, T was replaced by C, resulting in a leucine to proline substitution. Two family members had the mutation in two distinct generations. A new restriction site was created at this position and therefore enabled the development of a rapid diagnostic test using PCR. HERG wild type and mutant potassium channel mRNAs were then expressed in Xenopus laevis oocytes. CONCLUSION: This electrophysiological study suggests that coexpression of HERG wild type and mutant L564P results in a dominant negative effect of the mutation.

MRI findings in the parents and siblings of specifically language-impaired boys.

Four families that include a specifically language-impaired (SLI) boy were studied to test the hypothesis that developmental language disorders are biologically transmittable. A majority of the parents of the SLI boys had experienced communication difficulty (i.e., difficulty with speech, language, or academic skills) as children. Evidence of communication difficulty was paired on an individual basis with neuroanatomical data obtained through quantitative analysis of magnetic resonance imaging scans. Atypical perisylvian asymmetries were documented in a majority of the parents and were frequently associated with a history of communication difficulty. Atypical perisylvian asymmetries and disordered language skills were also documented for siblings of SLI boys. These findings suggest that atypical perisylvian asymmetries reflect a transmittable, biological factor that places some families at risk for language impairment.

Morphology of the inferior frontal gyrus in developmentally language-disordered adults.

The inferior frontal gyrus has traditionally been considered an important cortical region for language and may be important for understanding developmental language disorders. The morphology of the inferior frontal gyrus, as it appeared on T1-weighted sagittal magnetic resonance imaging (MRI) scans, was evaluated using a classification system that distinguished between seven basic morphological variants of the gyral and sulcal patterns in this region. This classification scheme was applied to the MRI scans of 41 neurologically normal adult subjects. To examine the relation between sulcal morphology and subject status, these subjects were sorted first by family history for developmental language disorders and then resorted by expression of behavioral signs consistent with a diagnosis of this disorder as determined by standardized testing. Morphological types that included an extra sulcus in the inferior frontal gyrus were statistically associated with the behaviorally based classification of subjects, but not with a positive family history for developmental language disorders. Because gyral patterns are prenatally determined, this finding is consistent with the theory that altered prenatal development contributes to the expression of a developmental language disorder.

Anatomical correlates of normal and impaired language in a set of dizygotic twins.

This report presents findings for a set of dizygotic twins at age 4 years 9 months. The male was diagnosed as specifically language impaired. For both children, the left-right perisylvian configuration was atypical. Only the male's configuration was symmetrical, a finding in line with autopsy data reported for subjects with "developmental dyslexia" who also may have had a form of language impairment. In addition, the male had an atypical (L greater than R) configuration of the cerebral hemispheres, a finding not seen in his twin, or in a series of volunteers without a history of developmental language impairment. The in utero effects of gonadal hormones that may account for these findings are discussed.

MRI findings in boys with specific language impairment.

Magnetic resonance imaging scans of specifically language-impaired (SLI) boys were examined to determine whether atypical cerebral findings could be documented in children whose primary deficits were in language skills. Clinical examination of the scans failed to reveal any visually obvious lesions or abnormalities. In contrast, measurement of the scans revealed atypical perisylvian asymmetries in most of these subjects. The distribution of perisylvian asymmetries in SLI subjects was significantly different from the distribution in controls (p less than .01). Measurement of other brain regions revealed that extraperisylvian areas were occasionally deviant in individual SLI subjects; but no one region was consistently deviant across the SLI group. Thus, only atypical perisylvian asymmetries were linked to the language disorder. These neuroanatomical findings suggest that a prenatal alteration of brain development underlies specific language impairment.

Criteria for SLI: the Stark and Tallal legacy and beyond.

Since it first appeared, the Stark and Tallal (1981 ) criteria for the selection of children with specific language impairment (SLI) has had a profound influence on research with this population. A review of the recent literature indicates that these criteria continue to be used, in part or in whole, in current research. However, the recent literature also provides illustrations of the use and interpretations of norm-referenced tests that can serve to update current best practices in subject selection. The original criteria for IQ and language test scores, along with their more recent adaptations, are reconsidered in light of current information on the use of tests with SLI.

Short-term and working memory differences in language/learning disabled and normal adults.

Fifteen adults who reported a childhood history of speech-language and/or learning disability (L/LD) were tested on two verbal memory tasks. Their performance on sentence repetition and reading span measures was compared with that of a matched control group who reported no childhood history of L/LD. Results indicated statistically significant group performance differences on both short-term and working memory tasks. This suggests that verbal memory difficulties may be a longterm component of L/LD.

IQ variability in children with SLI: implications for use of cognitive referencing in determining SLI.

The practice of cognitive referencing assumes that IQ scores can be used as a measure of intellectual potential from which language scores may deviate. To test the validity of this assumption the WISC scores of children with specific language impairment were compared over time. The variability of WISC scores from children with SLI from their initial evaluation and from the federally-mandated three year re-evaluation was analyzed. Significant differences in the performance scale scores were found. This indicates that the IQ scores of these children are more properly interpreted as reflecting current abilities rather than potential for language learning. This further calls into question the practice of cognitive referencing as a method of determining the presence of a language impairment, eligibility for services, and the service delivery model for which a child qualifies.

Bound-morpheme skills in the oral language of school-age, language-impaired children.

Bound-morphine skills of school-age, language-impaired (LI) children were explored with three tasks designed to assess multiple dimensions of this component of language. Ten English-speaking, school-age LI children (Mean age: 10:3) and ten children with normal language (Mean age: 9:9) served as subjects. A two-way analysis of variance revealed significant group differences. Fisher a priori testing documented significant group differences for a measure of English bound-morpheme skill levels, a measure of ability to generalize English bound-morphemes to novel words, and a measure of ability to learn novel bound-morphemes attached to novel words. The findings indicate that core features of developmental language impairment in preschool children--poor ability to learn, to use, and to generalize bound-morphemes--are also present in school-age, LI children.

Relations among verbal and nonverbal cognitive skills in normal language and specifically language-impaired children.

This study tested the hypothesis that specifically language-impaired (SLI) children have a qualitatively different cognitive system from that of normal language (NL) children. Twenty NL and 20 SLI children between the ages of 4:2 (years:months) and 5:11 were presented with experimental language-learning measures, experimental nonverbal measures, and verbal and nonverbal norm-referenced tests. A confirmatory analysis of the covariance matrix structures of the two subject groups indicated that relations among cognitive skills differed between NL and SLI children. In addition, a planned comparison indicated that the relation between nonverbal rule-induction and novel bound-morpheme learning differed significantly between groups. The findings indicate that a "qualitative-differences" model of specific language impairment better accounts for the co-occurrence of poor verbal and poor nonverbal cognitive skills in SLI children than a "low-normal" model.

Right hemisphere contribution to developmental language disorder: Neuroanatomical and behavioral evidence.

UNLABELLED: Developmental language disorder (DLD) is identified by virtue of the verbal deficits that define it. However, numerous studies have also documented nonverbal deficits in this population. This study attempts to explain the co-occurrence of both verbal and nonverbal deficits in this population from a brain-based perspective. Two samples of adults selected for DLD were compared with subjects without such a history on verbal and nonverbal skills in exploratory and confirmatory studies. Subjects also received MRI scans, which were used to determine the relation between left- and right-hemisphere regions hypothesized to relate to the behavioral skills tested. Results revealed replicable differences between groups on both verbal and nonverbal tasks. In addition, a significant association between performance on tests sensitive to facial affect and spatial rotation with the gray matter volume within the right supramarginal gyrus was found in both samples. These results support the hypothesis of a right hemisphere contribution to the profile of DLD. LEARNING OUTCOMES: As a result of this activity, the participant will be able to describe evidence in support of a role for the right hemisphere in DLD.