Biomedical subjects

Robert M Friedman

Publications and source records attributed to Robert M Friedman.

8 recordsLinked to original sources

PubMed2006

Identification of proteins immunologically related to interferon regulatory factor-1 that bind with interferon regulatory factor element.

Interferon regulatory factor (IRF)-1 expression was surveyed in nontransformed and oncogene-transformed mouse fibroblasts, using Western immunoblot with an IRF-1-specific antiserum, to examine possible differences resulting from cellular transformation. Ten additional proteins that reacted with the IRF-1 antibody and that underwent specific competition by peptide antigen were observed in extracts of both nontransformed and oncogene-transformed cell lines. Cross-reacting proteins were also observed in mouse macrophage extracts. Protein was captured from fibroblast nuclear extracts, using oligonucleotides representing IRF-binding sequences linked to magnetic beads. Captured proteins were eluted and analyzed by immunoblot with anti-IRF-1. Along with 43-kDa IRF-1, 4 of the 7 nuclearly located cross-reacting proteins (97, 90, 66, and 33 kDa) were found to complex with the IRF binding element. These proteins, with an epitope in common with the IRF-1 C-terminal region and IRF element DNA sequence-binding capability, may represent new members of the IRF family.

Animals↗

PubMed2006

Unlicensed residential programs: the next challenge in protecting youth.

Over the past decade in the United States, the number of private residential facilities for youth has grown exponentially, and many are neither licensed as mental health programs by states, nor accredited by respected national accrediting organizations. The Alliance for the Safe, Therapeutic and Appropriate use of Residential Treatment (A START) is a multi-disciplinary group of mental health professionals and advocates that formed in response to rising concerns about reports from youth, families and journalists describing mistreatment in a number of the unregulated programs. This article summarizes the information gathered by A START regarding unregulated facilities. It provides an overview of common program features, marketing strategies and transportation options. It describes the range of mistreatment and abuse experienced by youth and families, including harsh discipline, inappropriate seclusion and restraint, substandard psychotherapeutic interventions, medical and nutritional neglect, rights violations and death. It reviews the licensing, regulatory and accrediting mechanisms associated with the protection of youth in residential programs, or the lack thereof. Finally, it outlines policy implications and provides recommendations for the protection of youth and families who pursue residential treatment.

Accreditation↗

PubMed2005

Mechanisms of deregulation of IFN regulatory factor-1 in ras-transformed fibroblasts.

Interferon (IFN) regulatory factor-1 (IRF-1) deregulation in ras-transformed mouse fibroblasts (RS485) was studied. Treatment with the proteasome inhibitor MG132 did not alter the constitutive IRF-1 protein levels in RS485 but significantly increased them in nontransformed NIH 3T3 cells at 4 h after serum stimulation of synchronized cultures. Because IRF-1 protein levels in NIH 3T3 are minimal at 4 h after serum starvation, the cyclic expression of IRF-1 in NIH 3T3 appears to be partially due to proteasome activity; however, proteasome activity in RS485 did not appear to be defective. In NIH 3T3 and RS485 cells treated with cycloheximide, there were similar rapid drops in IRF-1 protein levels, and the addition of MG132 along with cycloheximide prevented protein loss in both cell lines. Northern blot analyses of synchronized cultures showed that the IRF-1 message closely mirrored the protein expression pattern in both NIH 3T3 and RS485 cells. In synchronized cells treated with the transcription inhibitor actinomycin D, IRF-1 mRNA half-life was only marginally longer in ras-transformed fibroblasts than in the nontransformed cells, and this difference would contribute minimally to protein overexpression. These findings indicate that IRF-1 deregulation in RS485 cells occurs primarily at the transcriptional level.

Animals↗

PubMed2004

Modality maps within primate somatosensory cortex.

The sensations of pressure, flutter, and vibration are psychophysically distinct tactile modalities produced by frequency-specific vibrotactile stimulation of different mechanoreceptors in the skin. The information coded by the different low-threshold mechanoreceptors are carried by anatomically and electrophysiologically distinct pathways that remain separate at least up to and including the input stage of primary somatosensory cortex (SI) in primates, area 3b. Little is known about the functional organization of tactile representation beyond that stage. By using intrinsic optical imaging methods to record from area 1, the second processing stage of SI, we present evidence that pressure, flutter, and vibratory stimuli activate spatially distinct cortical domains in area 1, further strengthening the foundation for modality-specific processing streams in SI. These modality domains exhibit an organization that is unlike the discontinuous modality maps in visual area V2 but more like the continuous visual orientation maps in V1. The results demonstrate that psychophysically distinct sensory modalities can have fundamentally different modes of cortical representation.

Animals↗

PubMed2004

Intraoperative optical imaging of human face cortical topography: a case study.

We used intrinsic signal optical imaging to obtain maps of human somatosensory cortex during electrocutaneous stimulation of the face during a neurosurgical procedure for epilepsy. We found that human face somatotopy is organized like the macaque or cebus monkey, with peri-orbital skin located medial to peri-buccal skin, and that cortical magnification in the human is comparable to that in non-human primates. This study demonstrates that intrinsic signal imaging can be performed on humans during operative procedures with sufficient spatial resolution to reveal high-resolution topographic maps.

Adult↗

PubMed2003

Optical imaging of a tactile illusion in area 3b of the primary somatosensory cortex.

In the tactile funneling illusion, the simultaneous presentation of brief stimuli at multiple points on the skin produces a single focal sensation at the center of the stimulus pattern even when no physical stimulus occurs at that site. Consistent with the funneling percept, we show with optical imaging in area 3b of the primary somatosensory cortex (SI) that simultaneous stimulation of two fingertips produces a single focal cortical activation between the single fingertip activation regions. Thus, in contrast to traditional views of the body map, topographic representation in the SI reflects the perceived rather than the physical location of peripheral stimulation.

Adult↗

PubMed2003

Deregulated expression of interferon regulatory factor-1 in oncogene-transformed mouse fibroblasts.

Interferon (IFN) regulatory factor-1 (IRF-1) is a transcription factor that has been historically associated with type I IFN activation and antioncogenic properties. We studied IRF-1 expression and DNA-binding capacity in nontransformed and transformed mouse fibroblasts. A 43-kDa nuclear IRF-1 protein was expressed biphasically during the cell cycle in primary mouse embryo fibroblasts, nontransformed NIH 3T3 cells, and ras revertants. IRF-1 expression became constitutive in ras-transformed NIH 3T3 cells and in cells transformed by oncogenes ets, fes, fos, her-2/neu, met, mos, raf, or trk, suggesting that deregulated IRF-1 expression may be associated with loss of growth control. Lysyl oxidase (LO), a ras suppressor that is downregulated in ras transformants, is an IRF-1 target gene, but it is not stimulated by abundant IRF-1 present in transformants, while another IRF-1 target gene (iNOS) is transcribed. IRF-1 from either normal or ras-transformed cells bound to IRF elements in the IFN-beta and LO promoters. IRF-1 in transformants can, therefore, bind to but not transactivate the LO promoter, and the presence of IRF-1 is not sufficient to suppress ras transformation. LO expression may effect the regulated expression of IRF-1: a ras revertant, which was generated by stable transfection of LO cDNA, regained the normal biphasic IRF-1 pattern. A mainly cytoplasmic, constitutively expressed 46-kDa protein with immunologic identity to the 43-kDa nuclear IRF-1 was also present in normal and transformed cells, but as it did not bind to the IRF elements, its function is unclear.

3T3 Cells↗

PubMed2002

Neural coding of the location and direction of a moving object by a spatially distributed population of mechanoreceptors.

A neural code for the location and direction of an object moving over the fingerpad was constructed from the responses of a population of rapidly adapting type I (RAs) and slowly adapting type I (SAs) mechanoreceptive nerve fibers. The object was either a sphere with a radius of 5 mm or a toroid with radii of 5 mm on the major axis and either 1 or 3 mm on the minor axis. The object was stroked under constant velocity and contact force along eight different linear trajectories. The spatial locations of the centers of activity of the population responses (PLs) were determined from nonsimultaneously recorded responses of 99 RAs and 97 SAs with receptive fields spatially distributed over the fingerpad of the anesthetized monkey. The PL at each moment during each stroke was used as a neural code of object location. The angle between the direction of the trajectory of the PL and mediolateral axis was used to represent the direction of motion of the object. The location of contact between the object and skin was better represented in SA than in RA PLs, regardless of stroke direction or object curvature. The PL representation of stroke direction was linearly related to the actual direction of the object for both RAs and SAs but was less variable for SAs than for RAs. Both the SA and RA populations coded spatial position and direction of motion at acuities similar to those obtained in psychophysical studies in humans.

Animals↗