PubMed HealthSearch

Biomedical subjects

B Cohen

Publications and source records attributed to B Cohen.

At least 19 recordsLinked to original sources

Soluble interferon-alpha receptor molecules are present in body fluids.

Soluble forms of the interferon-alpha receptor (sIFN-alpha R) were identified in human serum and urine by Western blotting with monoclonal antibodies (MAb) directed against IFN-alpha R, and by immunoprecipitation (Iptn) of a covalently cross-linked complex of IFN-alpha R and [125I]IFN-alpha with anti IFN-alpha MAb. Elevated levels of sIFN-alpha R were found in sera of hairy cell leukemia patients. The soluble receptor from serum migrated as a 55 kDa protein in SDS-PAGE, and, as expected, the cross-linked product migrated as a 75 kDa protein. The soluble receptor from urine was found to be a protein of mol. wt. 45 kDa and its cross-linked complex migrated as a 65 kDa protein. The calculated mol. wt. of the entire extracellular domain of the IFN-alpha R prior to post-translational modifications is 47,000. Since there are 12 potential glycosylation points in this extracellular domain, its actual mol. wt. may be as high as 70,000 Da. It is therefore concluded that sIFN-alpha R molecules, corresponding to truncated forms of the extracellular domain of the cell surface IFN-alpha R, are present in human serum and in normal human urine.

Animals

Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less.

Homeotic genes encode transcription factors that are thought to specify segmental identity by regulating expression of subordinate genes. Limb development is repressed in the abdominal segments of the Drosophila embryo by the hometic genes of the Bithorax complex (BX-C). Localized expression of the homeobox gene Distal-less (DII) is required for leg development in thoracic segments. We have identified a minimal cis-regulatory enhancer element that directs DII expression in the larval leg primordia. We present evidence that the BX-C proteins repress DII expression in abdominal segments by binding to a small number of specific sites in this element. Mutating these sites eliminates BX-C protein binding and renders the element insensitive to BX-C-mediated repression in vivo. Repression of limb development in the abdomen appears to be controlled at the DII enhancer. Thus DII may serve as a downstream target gene through which the homeotic genes control abdominal segment identity in the Drosophila embryo.

Amino Acid Sequence

L-baclofen-sensitive GABAB binding sites in the medial vestibular nucleus localized by immunocytochemistry.

L-Baclofen-sensitive GABAB binding sites in the medial vestibular nucleus (MVN) were identified immunocytochemically and visualized ultrastructurally in L-baclofen-preinjected rats and monkeys, using a mouse monoclonal antibody with specificity for the p-chlorophenyl moiety of baclofen. Saline-preinjected animals showed no immunostain. In drug-injected animals, there was evidence for both pre- and postsynaptic GABAergic inhibition in MVN mediated by GABAB receptors. These neural elements could be utilized in control of velocity storage in the vestibulo-ocular reflex.

Animals

Spatial orientation of the vestibular system.

1. A simplified three-dimensional state space model of visual vestibular interaction was formulated. Matrix and dynamical system operators representing coupling from the semicircular canals and the visual system to the velocity storage integrator were incorporated into the model. 2. It was postulated that the system matrix for a tilted position was a composition of two linear transformations of the system matrix for the upright position. One transformation modifies the eigenvalues of the system matrix while another rotates the pitch and roll eigenvectors with the head, while maintaining the yaw axis eigenvector approximately spatially invariant. Using this representation, the response characteristics of the pitch, roll, and yaw eye velocity were obtained in terms of the eigenvalues and associated eigenvectors. 3. Using OKAN data obtained from monkeys and comparing to the model predictions, the eigenvalues and eigenvectors of the system matrix were identified as a function of tilt to the side or of tilt to the prone positions, using a modification of the Marquardt algorithm. The yaw eigenvector for right-side-down tilt and for downward pitch cross-coupling was approximately 30 degrees from the spatial vertical. For the prone position, the eigenvector was computed to be approximately 20 degrees relative to the spatial vertical. For both side-down and prone positions, oblique OKN induced along eigenvector directions generated OKAN which decayed to zero along a straight line with approximately a single time constant. This was verified by a spectral analysis of the residual sequence about the straight line fit to the decaying data. The residual sequence was associated with a narrow autocorrelation function and a wide power spectrum. 4. Parameters found using the Marquardt algorithm were incorporated into the model. Diagonal matrices in a head coordinate frame were introduced to represent the direct pathway and the coupling of the visual system to the integrator. Model simulations predicted the behavior of yaw and pitch OKN and OKAN when the animal was upright, as well as the cross-coupling in the tilted position. The trajectories in velocity space were also accurately simulated. 5. There were similarities between the monkey eigenvectors and human perception of the spatial vertical. For side-down tilts and downward eye velocity cross-coupling, there was only an Aubert (A) effect. For upward eye velocity cross-coupling there were both Müller (E) and Aubert (A) effects. The mean of the eigenvectors for upward and downward eye velocities overlay human 1 x g perceptual data.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The nucleus of the optic tract. Its function in gaze stabilization and control of visual-vestibular interaction.

1. Electrical stimulation of the nucleus of the optic tract (NOT) induced nystagmus and after-nystagmus with ipsilateral slow phases. The velocity characteristics of the nystagmus were similar to those of the slow component of optokinetic nystagmus (OKN) and to optokinetic after-nystagmus (OKAN), both of which are produced by velocity storage in the vestibular system. When NOT was destroyed, these components disappeared. This indicates that velocity storage is activated from the visual system through NOT. 2. Velocity storage produces compensatory eye-in-head and head-on-body movements through the vestibular system. The association of NOT with velocity storage implies that NOT helps stabilize gaze in space during both passive motion and active locomotion in light with an angular component. It has been suggested that "vestibular-only" neurons in the vestibular nuclei play an important role in generation of velocity storage. Similarities between the rise and fall times of eye velocity during OKN and OKAN to firing rates of vestibular-only neurons suggest that these cells may receive their visual input through NOT. 3. One NOT was injected with muscimol, a GABAA agonist. Ipsilateral OKN and OKAN were lost, suggesting that GABA, which is an inhibitory transmitter in NOT, acts on projection pathways to the brain stem. A striking finding was that visual suppression and habituation of contralateral slow phases of vestibular nystagmus were also abolished after muscimol injection. The latter implies that NOT plays an important role in producing visual suppression of the VOR and habituating its time constant. 4. Habituation is lost after nodulus and uvula lesions and visual suppression after lesions of the flocculus and paraflocculus. We postulate that the disappearance of vestibular habituation and of visual suppression of vestibular responses after muscimol injections was due to dysfacilitation of the prominent NOT-inferior olive pathway, inactivating climbing fibers from the dorsal cap to nodulouvular and flocculoparafloccular Purkinje cells. The prompt loss of habituation when NOT was inactivated, and its return when the GABAergic inhibition dissipated, suggests that although VOR habituation can be relatively permanent, it must be maintained continuously by activity of the vestibulocerebellum.

Animals

The representation of the spatial vertical in human optokinetic nystagmus.

With our stimulus conditions we were unable to record more than 2-3 beats of OKAN; therefore direct comparison to the data recorded from monkeys is not possible. We did, however, see cross-coupling in OKN. In monkeys, cross-coupling predominates in OKAN, indicating that velocity storage underlies this phenomenon. We consistently saw the axis of response shift towards the spatial vertical. This implies that although OKAN was weak, velocity storage contributed a representation of the spatial vertical to OKN that is dependent on the axis of the head or body with respect to gravity.

Eye Movements

The microstructural tensile properties and biochemical composition of the bovine distal femoral growth plate.

The tensile properties of distal femoral growth plates from 12-month-old cows were determined on uniformly prepared straight bone-growth plate-bone specimens (7 x 7 mm2 in cross-section) from predetermined anatomical sites on the physis. Each specimen was distracted to failure using a computer-controlled servo-hydraulic testing machine at a strain rate of 0.004 s-1. It was found that the exponential constitutive law, using finite deformation formulation for strain, provides an excellent description of the stress-strain behavior of all the specimens up to the point of failure. The ultimate stress and both tangent moduli (i.e., the toe region tangent modulus and the tangent modulus calculated at 75% of ultimate strain) varied with anatomical site. The anterior region was the strongest, followed by the posterior/lateral. The anterior and posterior/lateral regions were also the stiffest, whereas the posterior/medial and center regions were the weakest and most compliant. The bone-growth plate-bone specimen exhibited a low ultimate strain (13.8% +/- 6%) that did not vary significantly throughout the growth plate. This result suggests that disruption of the physis may occur in vivo even at the lower distractions currently recommended for the clinical chondrodiatasis procedure for leg lengthening. The biochemical composition of the growth plate in the anatomical regions correlated well with the tensile properties. There was a greater collagen content in the regions that were the stiffest and strongest. The gross morphology of the growth plate of the bovine distal femur is also described in this study. There is a regular pattern to the undulations of the physis at several dimensional levels. Histologic findings showed that orientation of the hypertrophic cell columns and transphyseal septa are aligned nearly parallel to the longitudinal axis of the diaphyseal shaft. This column orientation is not affected by the undulation of the primary contour of the physis, which at certain locations may be inclined as much as 60 degrees relative to the diaphyseal axis. The orientation of the hypertrophic cell columns appears to be one of the dominant microstructural features influencing the tensile behavior of the bone-growth plate-bone specimens.

Animals

Nystagmus induced by electrical stimulation of the vestibular and prepositus hypoglossi nuclei in the monkey: evidence for site of induction of velocity storage.

Electrical stimulation of the vestibular nuclei (VN) and prepositus hypoglossi nuclei (PPH) of alert cynomolgus monkeys evoked nystagmus and eye deviation while they were in darkness. At some sites in VN, nystagmus and after-nystagmus were induced with characteristics suggesting that velocity storage had been excited. We analyzed these responses and compared them to the slow component of optokinetic nystagmus (OKN) and to optokinetic after-nystagmus (OKAN). We then recorded unit activity in VN and determined which types of nystagmus would be evoked from the sites of recording. Nystagmus and eye deviations were also elicited by electrical stimulation of PPH, and we characterized the responses where unit activity was recorded in PPH. Horizontal slow phase velocity of the VN "storage" responses was contralateral to the side of stimulation. The rising time constants and peak steady-state velocities were similar to those of OKN, and the falling time constants of the after-nystagmus and of OKAN were approximately equal. Both the induced after-nystagmus and OKAN were habituated by stimulation of the VN. When horizontal after-nystagmus was evoked with animals on their sides, it developed yaw and pitch components that tended to shift the vector of the slow phase velocity toward the spatial vertical. Similar "cross-coupling" occurs for horizontal OKAN or for vestibular post-rotatory nystagmus elicited in tilted positions. Thus, the storage component of nystagmus induced by VN stimulation had the same characteristics as the slow component of OKN and the VOR. Positive stimulus sites for inducing nystagmus with typical storage components were located in rostral portions of VN. They lay in caudal ventral superior vestibular nucleus (SVN), dorsal portions of central medial vestibular nucleus (MVN) caudal to the abducens nuclei and in adjacent lateral vestibular nucleus (LVN). More complex stimulus responses, but with contralateral after-nystagmus, were induced from surrounding regions of ventral MVN and LVN, rostral descending vestibular nucleus and the marginal zone between MVN and PPH. Vestibular-only (VO), vestibular plus saccade (VPS) and tonic vestibular pause (TVP) units were identified by extracellular recording. Stimulation near type I lateral and vertical canal-related VO units elicited typical "storage" responses with after-nystagmus in 23 of 29 tracks (79%). Stimulus responses were more complex from the region of neurons with oculomotor-related signals, i.e., TVP or VPS cells, although after-nystagmus was also elicited from these sites. Effects of vestibular nerve and nucleus stimulation were compared.(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve

Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum.

We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (approximately 5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore x 2.2 magnifying or x 0.5 reducing lenses. Adaptation occurred rapidly and reached about +/- 30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6-8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h0).(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization

Monoclonal antibodies for ultrastructural visualization of L-baclofen-sensitive GABAB receptor sites.

Monoclonal antibodies were raised against the L-enantiomer of baclofen conjugated by glutaraldehyde to keyhole limpet hemocyanin. Hybridoma clones were selected for their stability and their production of high titers of antibodies directed against the p-chlorophenyl moiety of the L-baclofen molecule. The chosen antibody showed no cross-reactivity with conjugates of GABA and other neurotransmitters to human or bovine serum albumin. Specificity was further confirmed by the ability of L-baclofen-HCl to inhibit the binding of the antibody to L-baclofen-bovine serum albumin conjugate. Immunocytochemical studies were conducted on brain tissue from rats and monkeys injected with baclofen to localize baclofen-sensitive GABAB receptor sites. In these animals, the molecular layer of cerebellar cortex was clearly immunostained and the granular layer showed only some pale immunoreactivity. Ultrastructural observations were conducted in cerebellar cortex, as well as in the substantia nigra and the vestibular nuclei. Discrete labeling of neuronal profiles was observed in these structures, and both immunoperoxidase and colloidal gold methods were employed successfully. Material from saline-injected control animals showed no immunoreactivity at both light and electron microscopic levels. We conclude that the anti-L-baclofen antibody preferentially recognizes the p-chlorophenyl moiety of the baclofen molecule. Antibodies of such specificity are useful tools for the ultrastructural localization of baclofen-sensitive GABAB receptor sites. In general, antibodies directed against accessible moieties of specific neuroactive substances may serve as valuable markers for their sites of action.

Animals

Extension-supination sign in prearthroscopic elbow distension.

A clinical sign of extension and supination of the elbow is described after prearthroscopic distension with fluid. When elicited, intra-articular fluid placement is indicated, assisting correct location of the arthroscope within the joint.

Arthroscopy

Arthroscopic resection of chondroblastoma of the knee.

We present a case of chondroblastoma of the upper tibia treated by complete arthroscopic excision. The diagnostic difficulties raised by the case are discussed. This method of treatment has not, to our knowledge, been reported in the literature.

Adolescent

Arteriovenous fistula after arthroscopic synovectomy in a patient with haemophilia.

Arteriovenous fistula is a rare complication of arthroscopy. We report a human immunodeficiency virus-positive person with haemophilia who 19 months after an arthroscopic synovectomy of the knee presented with increasingly frequent haemarthroses and a palpable thrill over the knee. Angiography confirmed an arteriovenous fistula. The patient was successfully treated by surgical ligation of the communicating vessels. The literature regarding vascular injuries after arthroscopy of the knee is reviewed.

Adolescent

Subluxation of the posterior stabilized total knee arthroplasty. A report of two cases.

There has been only one previous report of dislocation of a posteriorly stabilized total knee arthroplasty. The authors present two further cases of subluxation of this prosthesis and report a method of accomplishing reduction that could not otherwise be achieved by conventional techniques. The current design of this prosthesis enabled revision of the polyethylene tibial component to be undertaken without removal of the cemented metal-backing tray, an advantage not previously appreciated.

Aged