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Biomedical subjects

D E Feldman

Publications and source records attributed to D E Feldman.

31 records · Page 2Linked to original sources
PubMed1999

Smoking. A risk factor for development of low back pain in adolescents.

STUDY DESIGN: A prospective, repeated-measures cohort design with high school students from Montreal, Canada. OBJECTIVES: To determine whether smoking was a risk factor for the development of low back pain or other musculoskeletal pain in a cohort of adolescents. SUMMARY OF BACKGROUND DATA: Smoking has been associated with low back pain in adults. Many adolescents smoke, and the prevalence of low back pain in this age group is 30%. A history of low back pain is predictive of future problems. METHODS: A total of 502 students from grades 7 to 9 were assessed from 3 schools. Data were collected at 3 times: at the beginning of the study, at 6 months, and at the end of a 12-month period. Students responded to a questionnaire addressing musculoskeletal health and life-style factors, which included smoking. Measurements of height, weight, trunk and leg flexibility, and trunk strength were obtained. Low back pain occurring at a frequency of at least once a week in the past 6 months was defined as the outcome. Multivariate methods were used to model the repeated-measures dichotomous outcome as a function of smoking and other covariates. RESULTS: Smokers experienced low back pain more than nonsmokers (odds ratio, 2.4; 95% confidence interval, 1.3-6.0). There was also a dose-response relationship between amount smoked and development of low back pain. Smokers tended to experience more upper limb or lower limb pain than nonsmokers, although this result was not significant. CONCLUSIONS: Smoking was found to increase the risk for low back pain in this cohort of adolescents.

Adolescent↗
PubMed1999

Formation of the VHL-elongin BC tumor suppressor complex is mediated by the chaperonin TRiC.

von Hippel-Lindau (VHL) disease is caused by loss of function of the VHL tumor suppressor protein. Here, we demonstrate that the folding and assembly of VHL into a complex with its partner proteins, elongin B and elongin C (herein, elongin BC), is directly mediated by the chaperonin TRiC/CCT. Association of VHL with TRiC is required for formation of the VHL-elongin BC complex. A 55-amino acid domain of VHL is both necessary and sufficient for binding to TRiC. Importantly, mutation or deletion of this domain is associated with VHL disease. We identified two mutations that disrupt the normal interaction with TRiC and impair VHL folding. Our results define a novel role for TRiC in mediating oligomerization and suggest that inactivating mutations can impair polypeptide function by interfering with chaperone-mediated folding.

Chaperonins↗
PubMed1999

Synaptic plasticity at thalamocortical synapses in developing rat somatosensory cortex: LTP, LTD, and silent synapses.

Thalamocortical synaptic transmission in the rat's primary somatosensory (S1) cortex is modified by sensory experience during a critical period early in life. Despite the importance of such plasticity for the maturation of thalamocortical circuits, the synaptic basis of this plasticity is unknown. Here, we review evidence suggesting that long-term potentiation and depression (LTP and LTD) of thalamocortical synaptic transmission may be involved in this plasticity. In an in vitro slice preparation, thalamocortical synaptic responses exhibit N-methyl-D-aspartate (NMDA) receptor-dependent LTP and LTD during a developmental period similar to the critical period in vivo. The inability to induce LTP and LTD after the critical period may result in part from a developmental reduction in the duration of NMDA receptor currents. In addition, during the critical period many thalamocortical synapses exhibit NMDA receptor currents but no detectable AMPA receptor currents, and thus may be functionally silent at resting membrane potentials. LTP converts silent synapses to functional ones by causing the rapid appearance of AMPA currents. These observations suggest that thalamocortical synapses may be formed as silent synapses which are subsequently made functional by LTP. LTP and LTD may then regulate the efficacy of these functional synapses and thereby contribute to experience-dependent changes in S1 thalamocortical circuits.

Animals↗
PubMed1998

Pharmacological specialization of learned auditory responses in the inferior colliculus of the barn owl.

Neural tuning for interaural time difference (ITD) in the optic tectum of the owl is calibrated by experience-dependent plasticity occurring in the external nucleus of the inferior colliculus (ICX). When juvenile owls are subjected to a sustained lateral displacement of the visual field by wearing prismatic spectacles, the ITD tuning of ICX neurons becomes systematically altered; ICX neurons acquire novel auditory responses, termed "learned responses," to ITD values outside their normal, pre-existing tuning range. In this study, we compared the glutamatergic pharmacology of learned responses with that of normal responses expressed by the same ICX neurons. Measurements were made in the ICX using iontophoretic application of glutamate receptor antagonists. We found that in early stages of ITD tuning adjustment, soon after learned responses had been induced by experience-dependent processes, the NMDA receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP-5) preferentially blocked the expression of learned responses of many ICX neurons compared with that of normal responses of the same neurons. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked learned and normal responses equally. After long periods of prism experience, preferential blockade of learned responses by AP-5 was no longer observed. These results indicate that NMDA receptors play a preferential role in the expression of learned responses soon after these responses have been induced by experience-dependent processes, whereas later in development or with additional prism experience (we cannot distinguish which), the differential NMDA receptor-mediated component of these responses disappears. This pharmacological progression resembles the changes that occur during maturation of glutamatergic synaptic currents during early development.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Long-term depression at thalamocortical synapses in developing rat somatosensory cortex.

Sensory experience during an early critical period guides the development of thalamocortical circuits in many cortical areas. This process has been hypothesized to involve long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical synapses. Here, we show that thalamocortical synapses in rat barrel cortex can express LTD, and that LTD is most readily induced during a developmental period that is similar to the critical period for thalamocortical plasticity in vivo. Thalamocortical LTD is homosynaptic and dependent on activation of N-methyl-D-aspartate (NMDA) receptors. The age-related decline of LTD is not due to changes in inhibition nor to changes in NMDA receptor voltage dependence. Minimal stimulation experiments indicate that, unlike thalamocortical LTP, thalamocortical LTD is not associated with a significant change in failure rate. The existence of LTD and its developmental time course suggest that LTD, like LTP, may contribute to the refinement of thalamocortical inputs in vivo.

Animals↗
PubMed1997

An anatomical basis for visual calibration of the auditory space map in the barn owl's midbrain.

The map of auditory space in the external nucleus of the inferior colliculus (ICX) of the barn owl is calibrated by visual experience during development. ICX neurons are tuned for interaural time difference (ITD), the owl's primary cue for sound source azimuth, and are arranged into a map of ITD. When vision is altered by rearing owls with prismatic spectacles that shift the visual field in azimuth, ITD tuning in the ICX shifts adaptively. In contrast, ITD tuning remains unchanged in the lateral shell of the central nucleus of the inferior colliculus (ICCls), which provides the principal auditory input to the ICX, suggesting that the projection from the ICCls to the ICX is altered by prism-rearing. In this study, the topography of the ICCls-ICX projection was assessed in normal and prism-reared owls by retrograde labeling using biotinylated dextran amine. In juvenile owls at the age before prism attachment, and in normal adults, labeling patterns were consistent with a topographic projection, with each ICX site receiving input from a restricted region of the ICCls with similar ITD tuning. In prism-reared owls, labeling patterns were systematically altered: each ICX site received additional, abnormal input from a region of the ICCls where ITD tuning matched the shifted ITD tuning of the ICX neurons. These results indicate that anatomical reorganization of the ICCls-ICX projection contributes to the visual calibration of the ICX auditory space map.

Animals↗
PubMed1996

Newly learned auditory responses mediated by NMDA receptors in the owl inferior colliculus.

Alignment of auditory and visual receptive fields in the optic tectum of the barn owl (Tyto alba) is maintained through experience-dependent modification of auditory responses in the external nucleus of the inferior colliculus (ICX), which provides auditory input to the tectum. Newly learned tectal auditory responses, induced by altered visual experience, were found to be pharmacologically distinct from normal responses expressed at the same tectal sites. N-methyl-D-aspartate (NMDA) receptor antagonists administered systemically or applied locally in the ICX reduced learned responses more than normal responses. This differential blockade was not observed with non-NMDA or broad-spectrum antagonists. Thus, NMDA receptors preferentially mediate the expression of novel neuronal responses induced by experience during development.

2-Amino-5-phosphonovalerate↗
PubMed1995

Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch.

The first cells generated during development of the vertebrate retina are the ganglion cells, the projection neurons of the retina. Although they are one of the most intensively studied cell types within the central nervous system, little is known of the mechanisms that determine ganglion cell fate. We demonstrate that ganglion cells are selected from a large group of competent progenitors that comprise the majority of the early embryonic retina and that differentiation within this group is regulated by Notch. Notch activity in vivo was diminished using antisense oligonucleotides or augmented using a retrovirally transduced constitutively active allele of Notch. The number of ganglion cells produced was inversely related to the level of Notch activity. In addition, the Notch ligand Delta inhibited retinal progenitors from differentiating as ganglion cells to the same degree as did activated Notch in an in vitro assay. These results suggest a conserved strategy for neurogenesis in the retina and describe a versatile in vitro and in vivo system with which to examine the action of the Notch pathway in a specific cell fate decision in a vertebrate.

Alleles↗
PubMed1994

NMDA and non-NMDA glutamate receptors in auditory transmission in the barn owl inferior colliculus.

The pharmacology of auditory responses in the inferior colliculus (IC) of the barn owl was investigated by iontophoresis of excitatory amino acid receptor antagonists into two different functional subdivisions of the IC, the external nucleus (ICx) and the lateral shell of the central nucleus (lateral shell), both of which carry out important computations in the processing of auditory spatial information. Combined application of the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (AP5) and the non-NMDA receptor antagonist 6-cyano-5-nitroquinoxaline-2,3-dione (CNQX) significantly reduced auditory-evoked spikes at all sites in these two subdivisions, and completely eliminated responses at many locations. This suggests that excitatory amino acid receptors mediate the bulk, if not all, of auditory responses in the ICx and lateral shell. NMDA and non-NMDA receptors contributed differently to auditory responses in the two subdivisions. In the ICx, AP5 significantly reduced the number of auditory-evoked spikes at every site tested. On average, AP5 eliminated 55% of auditory-evoked spikes at multiunit sites and 64% at single-unit sites in this structure. In contrast, in the lateral shell, AP5 significantly reduced responses at less than half the sites tested, and, on average, AP5 eliminated only 19% of spikes at multiunit sites and 25% at single-unit sites. When the magnitude of response blockade produced by AP5 at individual multiunit sites was normalized to adjust for site-to-site differences in the efficacy of iontophoresed AP5 and CNQX, AP5 blockade was still significantly greater in the ICx than the lateral shell. CNQX application strongly reduced responses in both subdivisions. These data suggest that NMDA receptor currents make a major contribution to auditory responses in the ICx, while they make only a small contribution to auditory responses in the lateral shell. Non-NMDA receptor currents, on the other hand, contribute to auditory responses in both subdivisions, and mediate the bulk of auditory transmission in the lateral shell. The time course of the NMDA receptor contribution to ICx auditory responses and the dependence of this contribution on stimulus level were both examined in detail. AP5 preferentially blocked spikes late in ICx auditory responses, while CNQX blocked spikes equally throughout the responses. This pattern is consistent with a simple model in which slow NMDA receptor currents and faster non-NMDA receptor currents are both activated by auditory inputs to ICx neurons.

2-Amino-5-phosphonovalerate↗
PubMed1987

Risk factors for sleep disordered breathing in heterogeneous geriatric populations.

This cross-sectional, multivariate study investigated associations between sleep disordered breathing (SDB) and putative risk factors in a heterogeneous group of 720 individuals over the age of 50 years studied during all-night in-lab polysomnography. Results indicated that: aged men were more likely to show impaired respiration during sleep than aged women; excessive daytime somnolence and parasomniac symptoms (snoring, gasping during sleep) were associated with SDB but insomnia was not; obesity accounted for more variance in SDB than age per se, implying that the prevalence of SDB in some elderly persons could be related to the deposition of body fat seen as individuals grow older. All four risk factors (age, sex, obesity, and symptomatic status) were statistically significant and independent predictors of impaired respiration in sleep in the elderly.

Age Factors↗
PubMed1977

The submandibular triangle in radical neck dissection.

Various modifications of the standard radical neck dissection operation have been advocated since its original description. An ideal operation would offer maximum cure rates with minimal cosmetic and functional disturbance. The validity of removing the submandibular triangle contents as part of radical neck dissection was studied by analyzing the involvement of this region by metastatic squamous cell carcinomas of the head and neck. Only three of the 51 neck-dissection specimens that were examined contained metastases to submandibular triangle lymph nodes. The primary sites were nose, floor of mouth, and retromolar trigone. None of the 26 laryngeal tumors in this series had spread to the submandibular triangle. In the absence of palpable submandibular or upper, deep cervical lymph nodes, the contents of the submandibular triangle can probably be left undisturbed in radical neck dissections for laryngeal cancer.

Carcinoma, Squamous Cell↗