Biomedical subjects

David Friedman

Publications and source records attributed to David Friedman.

At least 37 records · Page 2Linked to original sources

PubMed2004

The Drosophila fragile X-related gene regulates axoneme differentiation during spermatogenesis.

Macroorchidism (i.e., enlarged testicles) and mental retardation are the two hallmark symptoms of Fragile X syndrome (FraX). The disease is caused by loss of fragile X mental retardation protein (FMRP), an RNA-binding translational regulator. We previously established a FraX model in Drosophila, showing that the fly FMRP homologue, dFXR, acts as a negative translational regulator of microtubule-associated Futsch to control stability of the microtubule cytoskeleton during nervous system development. Here, we investigate dFXR function in the testes. Male dfxr null mutants have the enlarged testes characteristic of the disease and are nearly sterile (>90% reduced male fecundity). dFXR protein is highly enriched in Drosophila testes, particularly in spermatogenic cells during the early stages of spermatogenesis. Cytological analyses reveal that spermatogenesis is arrested specifically in late-stage spermatid differentiation following individualization. Ultrastructurally, dfxr mutants lose specifically the central pair microtubules in the sperm tail axoneme. The frequency of central pair microtubule loss becomes progressively greater as spermatogenesis progresses, suggesting that dFXR regulates microtubule stability. Proteomic analyses reveal that chaperones Hsp60B-, Hsp68-, Hsp90-related protein TRAP1, and other proteins have altered expression in dfxr mutant testes. Taken together with our previous nervous system results, these data suggest a common model in which dFXR regulates microtubule stability in both synaptogenesis in the nervous system and spermatogenesis in the testes. The characterization of dfxr function in the testes paves the way to genetic screens for modifiers of dfxr-induced male sterility, as a means to efficiently dissect FMRP-mediated mechanisms.

Animals↗

PubMed2004

The old switcheroo: when target environmental sounds elicit a novelty P3.

OBJECTIVE: Novel environmental sounds that are task-irrelevant in the novelty oddball paradigm elicit the novelty P3 or P3a with a fronto-central scalp distribution, while pure tone task-relevant stimuli elicit a P3 with a posterior topography (P3b). To determine whether stimulus nature or its function in the task modulates scalp topography, the role of the two types of stimuli during the novelty oddball task was reversed. METHODS: Brain electrical activity was recorded while 12 young adults listened to frequent tones, infrequent tones, and infrequent environmental sounds. Subjects were not informed about the infrequent tones, but were instructed to press a reaction time (RT) button when they heard the infrequent environmental sounds. RESULTS: Despite the "novelty" nature of the tones, they were associated with a posterior scalp distribution typical of the P3b. Similarly, despite the "target" nature of the environmental sounds, they were associated with a fronto-central scalp topography typical of the P3a. CONCLUSIONS: These data suggest that the elicitation of a novelty P3 depends not only on task demands but also on the physical nature of the stimulus. SIGNIFICANCE: The brain's orienting response is modulated by the contextual environment as well as the physical properties of the eliciting stimulus.

Acoustic Stimulation↗

PubMed2004

A ghost of retrieval past: a functional network of alpha EEG related to source memory in elderly humans.

The electrophysiological data from a study of source memory in young and older adults were analyzed in the frequency domain in order to find functional networks of alpha band activity related to source memory performance and cortical reorganization with age. Participants were instructed to remember noun pairs embedded in sentences, with sentences grouped into two temporally distinct lists. At test, in response to noun probes, participants made old/new, followed by source (i.e., list) judgments. Lower band alpha electroencephalography (EEG) recorded during recognition and source retrieval epochs was analyzed using spatial covariance analysis [Hum. Brain Mapp. 2 (1994) 79; J.R. Moeller, C. Ghez, A. Antonini, M.F. Ghilardi, V. Dhawan, K. Kazumata, D. Eidelberg, Brain networks of motor behavior assessed by principal component analysis, in: R.E. Carson, M.E. Daube-Witherspoon, P. Herscovitch (Eds.), Quantitative Functional Brain Imaging with Positron Emission Tomography, Academic, San Diego, 1998]: significant activation patterns were found in source retrieval epochs. For young subjects, the regional covariance pattern involved coactivation of right anterior and left posterior electrode sites. Source retrieval performance was predicted by the subject difference in pattern expression between epochs involving correct and incorrect source attribution. The older adults also exhibited significant coactivation of the right anterior and left posterior electrode sites. However, no compensatory activation sites were identified for these elders who performed near chance in source retrieval. In this regard, we replicated the main functional difference between good and poor performing elders reported in a recent O-15 PET study of source retrieval in young and older subjects [Neuroimage 17 (2002) 1394]. These alpha band and O-15 PET findings complement the age group differences found in the time-domain (ERP) analysis of our EEG data [Psychol. Aging 14 (1999) 390]. We suggest that spatial covariance analyses of spectral EEG and MEG data will reveal new information about functional brain activity relevant to normal aging.

Adult↗

PubMed2004

Undercorrected refractive error in Singaporean Chinese adults: the Tanjong Pagar survey.

OBJECTIVE: To study the prevalence of undercorrected refractive error and associated sociodemographic factors among Singaporean Chinese adults. DESIGN: Cross-sectional, population-based survey. PARTICIPANTS: Singaporean Chinese adults aged 40 to 79 years (n = 1152). METHODS: The Singapore electoral register of Tanjong Pagar was used as a sampling frame, and disproportionate, stratified, clustered, random sampling was performed. There were 1717 eligible adults and 1232 (71.8%) participated. Analysis was performed among 1152 adults with complete habitual and best-corrected visual acuity data. MAIN OUTCOME MEASURE: Undercorrected refractive error was defined as improvement of better eye visual acuity of at least 2 lines or more with best possible refractive correction. RESULTS: The age- and gender-adjusted rate of undercorrected refractive error standardized directly by age and gender was 17.3% (95% confidence interval, 15.0, 19.5). Undercorrected refractive error rates were more common in older adults who had completed fewer years of education and in those who had cataract. People who did not wear spectacles tended to have poorer vision. CONCLUSIONS: The undercorrected refractive error rate among Singaporean Chinese is relatively common compared with data from other populations.

Adult↗

PubMed2004

Severe influenza B myocarditis and myositis.

OBJECTIVE: To report an influenza B infection with associated myocarditis and severe skeletal myositis. DESIGN: Case report. SETTING: Cardiac intensive care unit in a university-affiliated children's hospital. PATIENT: A 4-yr-old girl. RESULTS: The patient was successfully supported with extracorporeal membrane oxygenation for profound myocardial dysfunction and a combination of plasmapheresis and continuous venovenous hemodialysis for rhabdomyolysis and acute renal failure. CONCLUSIONS: This case provides a reminder that patients presenting with viral illness or myoglobinuria accompanied by renal failure, with or without associated myocarditis, may be demonstrating symptoms of influenza B.

Child, Preschool↗

PubMed2004

Classic and false memory designs: an electrophysiological comparison.

In false memory tasks new items either overlap with the semantic concepts of studied items (LURE) or do not (NEW). ERP differences between OLD and NEW items in false memory tasks have been interpreted as similar to episodic memory effects observed in classic recognition studies. However, NEW items in a false memory task can be rejected on the basis of semantic information alone, a strategy useless in classic tasks. Here a medial frontal (400 to 500 ms) episodic memory effect was revealed in both classic and false memory tasks, whereas a parietal (500 to 700 ms) episodic memory effect was found only in the classic task. In the false memory task a large, parietally focused positivity was evident for NEW items, assumed to reflect a targetlike response to new semantic information. The brain activity underlying false memory effects, therefore, cannot be interpreted as a straightforward example of that arising during a standard recognition task.

Adolescent↗

PubMed2003

Pictures and their colors: what do children remember?

Theories regarding children's reliability as witnesses suggest that children are more likely to confuse memories from different sources especially when the sources are highly similar. To investigate the developmental aspects of source retrieval, we measured brain electrical activity from children and adults while they retrieved content and source information. Similar brain responses among the age groups were found when participants were asked to retrieve content information. However, retrieval of source information improved with age and was accompanied by different patterns of brain potentials. The results implicate immaturity of frontal lobe structures in children's difficulty in retrieving source information.

Adolescent↗

PubMed2003

Cross-form conceptual relations between sounds and words: effects on the novelty P3.

In order for cross-form conceptual priming to occur, the brain must extract an amodal representation of the presented concept. To determine whether the novelty P3 would show such cross-form effects, novel, environmental sounds or their verbal equivalents were repeated two blocks after their first presentation in two cross-form conditions, word-sound (e.g., the word "pig" followed by the sound "oink") or sound-word. Conceptual repetition engendered an asymmetric reduction in novelty P3 amplitude, i.e., amplitude was reduced in the sound-word but not in the word-sound condition. The data suggest that the novelty P3 reflects an evaluative stage of processing in which some semantic information is extracted. However, the lack of amplitude reduction for the word-sound condition implies that, at least at the delays used here, repetition as a conceptually equivalent sound may have failed to make contact with the initial verbal concept.

Acoustic Stimulation↗

PubMed2003

Cataract after glaucoma filtration surgery.

PURPOSE: We reviewed the evidence regarding cataract incidence and progression after glaucoma surgery. DESIGN: Evidence-based review of available literature. METHODS: We performed a systematic review of relevant studies published in English. RESULTS: Reports of visually significant cataract after glaucoma surgery are supported by data from randomized clinical trials and large case series. CONCLUSIONS: Patients undergoing glaucoma surgery are at increased risk for the development and progression of cataract.

Cataract↗

PubMed2003

Cognition and aging: a highly selective overview of event-related potential (ERP) data.

An overview of highly selected cognitive aging investigations of deviance detection, episodic memory and working memory reveals two primary themes: (1) when variability in elderly samples has been assessed, it has proven useful in understanding age-related changes in cognition; and (2) there is a frontal lobe contribution to at least some age-related changes in cognition. However, there are too few ERP age-related investigations of individual differences to determine whether the changes in patterns of ERP responding can be deemed "compensatory" or "inefficient." It is suggested that, to the extent possible, future electrophysiological investigations of cognitive aging (as well as other physiological measurement techniques) include individual difference measures that will enable the determination of the implication of a given neural pattern in the genesis of a given, age-related behavioral outcome pattern.

Adolescent↗

PubMed2003

A randomized trial of visual impairment interventions for nursing home residents: study design, baseline characteristics and visual loss.

INTRODUCTION: Visual impairment among nursing home residents is higher than in community-dwelling elderly. The provision of eye care services may be beneficial to nursing home patients. Our project, a randomized trial of vision restoration and rehabilitation in nursing home residents, compares usual care to targeted interventions. In this paper, we present the baseline characteristics of our sample within the nursing homes. METHODS: Twenty-eight nursing homes on Maryland's Eastern Shore were matched in pairs by size and payment type. Each pair was randomized to usual care or targeted intervention. Habitual and best-corrected acuity was attempted, using standard letter symbol/charts and grating acuity charts. Visual impairment was vision in the better eye <20/40 on letter and/or grating acuity. The MiniMental State Examination (MMSE) was used to determine cognitive impairment. RESULTS: Of those participants eligible to be screened, 40% had severe cognitive impairment (MMSE score 0-9). No measure of acuity could be ascertained on 18% of eligibles. Among the 1305 persons with acuity data, 38% had presenting vision worse than 20/40. After refractive correction, 29% had visual impairment. There was no difference by race or gender in those with visual impairment, although they were older, compared to those without visual loss. CONCLUSIONS: The nursing home residents had high rates of both cognitive impairment and visual impairment, creating a challenging environment for visual intervention. By improving access to eye care within the context of the clinical trial, and changing either the magnitude of visual loss or the resultant impact on function, we hope to demonstrate a change in the quality of life for nursing home residents.

Aged↗

PubMed2003

Stimulus characteristics and task category dissociate the anterior and posterior aspects of the novelty P3.

The novelty P3 is an event-related potential component that is most often elicited by environmental sounds within the "novelty oddball" paradigm. Within the context of this paradigm, it is not clear if the novelty P3 can be elicited by deviant stimuli regardless of whether they serve as target or nontarget deviants, or to what extent the physical characteristics of the stimulus contributes to the amplitude of the novelty P3. The current study examines this issue by systematically switching target and nontarget deviants between environmental sounds and tonal stimuli. Participants were 36 young adults. Auditory stimuli were 48 unique tones and 48 unique environmental sounds presented under three experimental conditions. The results showed that target and nontarget deviants elicited novelty P3s with anterior and posterior aspects. The major determinant of the extent of the anterior aspect was the degree of difference between the physical characteristics of the deviant stimuli and the standards. By contrast, the major determinant of the posterior aspect was the task relevance of the deviant stimuli.

Acoustic Stimulation↗

PubMed2003

Auditory selective attention in young and elderly adults: the selection of single versus conjoint features.

The effects of aging on the behavioral and neurophysiological correlates of auditory selective attention were investigated when selection was between either unidimensional or multidimensional stimuli. Attentional processes were studied by recording event-related brain potentials (ERPs) from 16 young (M = 22 years) and 16 elderly adults (M = 74 years) while they detected target tones based on a single location cue or a conjunction of location and pitch cues. Performance declined from the single- to the conjoint-cue task for both age groups but more so for the elderly. The ERP data showed that both age groups used a hierarchical processing strategy to perform the conjoint-cue task, but processing of the pitch dimension took longer for the elderly than for the young. The ERP data also showed that the scalp distribution of a late aspect of the waveform was more restricted in both anterior and posterior directions for the elderly. This suggests that frontal-lobe dependent attentional processes may be less efficacious with aging.

Acoustic Stimulation↗

PubMed2003

Source memory for the color of pictures: event-related brain potentials (ERPs) reveal sensory-specific retrieval-related activity.

Remembering the context (i.e., source) in which an event occurred reveals episodic memory effects (EM) in the event-related brain potentials (ERP). In some verbal source memory experiments, a late prefrontal EM effect has been observed. In a different, pictorial source memory paradigm, a late, parieto-occipital EM effect was recorded. To assess whether these two EM effects stemmed from differences in task paradigms or from source-attribute differences, ERPs were recorded during source memory retrieval for object colors in two tasks. In the sequential task, old/new judgments were followed by source judgments (i.e., color). In the exclusion task, source memory judgments coincided with recognition judgments. For both tasks, late, parietao-occipital EM effects were observed. These findings suggest that it is not the nature of the task, but rather the perceptual characteristics of the source that lead to the presence of the parieto-occipital EM effect. The data further imply that memories for perceptual attributes such as color are stored in and retrieved from sensory-specific cortical areas.

Adult↗

PubMed2003

Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells.

The C1/RIPE3b1 (-118/-107 bp) binding factor regulates pancreatic-beta-cell-specific and glucose-regulated transcription of the insulin gene. In the present study, the C1/RIPE3b1 activator from mouse beta TC-3 cell nuclear extracts was purified by DNA affinity chromatography and two-dimensional gel electrophoresis. C1/RIPE3b1 binding activity was found in the roughly 46-kDa fraction at pH 7.0 and pH 4.5, and each contained N- and C-terminal peptides to mouse MafA as determined by peptide mass mapping and tandem spectrometry. MafA was detected in the C1/RIPE3b1 binding complex by using MafA peptide-specific antisera. In addition, MafA was shown to bind within the enhancer region (-340/-91 bp) of the endogenous insulin gene in beta TC-3 cells in the chromatin immunoprecipitation assay. These results strongly suggested that MafA was the beta-cell-enriched component of the RIPE3b1 activator. However, reverse transcription-PCR analysis demonstrated that mouse islets express not only MafA but also other members of the large Maf family, specifically c-Maf and MafB. Furthermore, immunohistochemical studies revealed that at least MafA and MafB were present within the nuclei of islet beta cells and not within pancreas acinar cells. Because MafA, MafB, and c-Maf were each capable of specifically binding to and activating insulin C1 element-mediated expression, our results suggest that all of these factors play a role in islet beta-cell function.

Amino Acid Sequence↗

PubMed2002

Interaction of intracellular beta amyloid peptide with chaperone proteins.

Expression of the human beta amyloid peptide (A beta) in transgenic Caenorhabditis elegans animals can lead to the formation of intracellular immunoreactive deposits as well as the formation of intracellular amyloid. We have used this model to identify proteins that interact with intracellular A beta in vivo. Mass spectrometry analysis of proteins that specifically coimmunoprecipitate with A beta has identified six likely chaperone proteins: two members of the HSP70 family, three alpha B-crystallin-related small heat shock proteins (HSP-16s), and a putative ortholog of a mammalian small glutamine-rich tetratricopeptide repeat-containing protein proposed to regulate HSP70 function. Quantitative reverse transcription-PCR analysis shows that the small heat shock proteins are also transcriptionally induced by A beta expression. Immunohistochemistry demonstrates that HSP-16 protein closely colocalizes with intracellular A beta in this model. Transgenic animals expressing a nonaggregating A beta variant, a single-chain A beta dimer, show an altered pattern of coimmunoprecipitating proteins and an altered cellular distribution of HSP-16. Double-stranded RNA inhibition of R05F9.10, the putative C. elegans ortholog of the human small glutamine-rich tetratricopeptide-repeat-containing protein (SGT), results in suppression of toxicity associated with A beta expression. These results suggest that chaperone function can play a role in modulating intracellular A beta metabolism and toxicity.

Alzheimer Disease↗

PubMed2002

Age-related changes in source memory retrieval: an ERP replication and extension.

Event-related potentials (ERPs) were recorded (62 scalp sites) from young (M=22) and older (M=66) adults during tests of item recognition and source memory, in a replication and extension of a previous study [Psychol. Aging 14 (1999) 390-413]. Participants studied two temporally distinct lists of sentences (each with two unassociated nouns). At test, in response to studied and unstudied nouns, participants made old/new, followed by source (i.e., list) judgments. Several measures were employed to enhance the source memory performance of the older adults. These were successful, as the old adults showed source memory performance comparable to that of the young subjects from the previous study (67%). Nonetheless, the younger adults significantly outperformed the older adults on measures of item and source memory performance. The ERPs revealed that both age groups showed a robust early, posterior-maximal episodic memory (EM) effect. However, despite their enhanced source memory performance, the ERPs of the old failed to show a robust late, right-prefrontal EM effect, which was again present in the ERPs of the young. By contrast, the older adults showed a central negative component not seen in the ERPs of the young. These results are consistent with the frontal lobe deficit hypothesis of aging and provide some evidence that old and young may use distinct cortical networks during source memory retrieval.

Adult↗

PubMed2002

Acute onset of Wegener's granulomatosis and diffuse alveolar hemorrhage treated successfully by extracorporeal membrane oxygenation.

Wegener's granulomatosis is a necrotizing granulomatous vasculitis involving the upper airway, lungs, and kidneys. Diffuse alveolar hemorrhage is a rare and life-threatening presentation of Wegener's granulomatosis. We report on a previously healthy 13-yr-old boy who presented with fulminant pulmonary hemorrhage leading to acute respiratory distress syndrome and was found to have Wegener's granulomatosis. The diagnosis was based on clinical, radiologic, serologic, and histologic manifestations. The therapeutic challenges and the modalities of support to sustain life until clinical remission are presented.

Journal Article↗