Biomedical subjects

C J Robinson

Publications and source records attributed to C J Robinson.

At least 19 recordsLinked to original sources

PubMed2000

Multimicroelectrode stimulation within the cat L6 spinal cord: influences of electrode combinations and stimulus interleave time on knee joint extension torque.

During multimicroelectrode stimulation within the cat L6 spinal cord, the number of electrodes activated, their separation distance, and the stimulus interleave time all influenced isometric knee joint extension torque. The torque evoked by stimulation with a three electrode combination could be enhanced or suppressed when compared with that evoked by single or paired electrode stimulation. A similar difference was noted when comparing two electrode combination versus single electrode stimulation. Relative fatigue was not improved significantly by interleaving the stimuli from two or three microelectrodes. Compared with the extension torque response evoked by noninterleaved stimulation, torque evoked by interleaved stimulation with the two microelectrode combination was decreased when the electrode distance was 2.0 mm or less and increased when the electrode distance was 3.0 mm. Designing an optimal stimulation strategy for multimicroelectrode spinal cord stimulation will be challenging and complex if a suppression effect among these electrodes is to be avoided. To reduce muscle fatigue, an asynchronous, interleaved strategy of stimulation may be required.

Animals↗

PubMed2000

Role of citrate synthase in aldosterone-mediated sodium reabsorption.

Aldosterone and other mineralocorticoids increase citrate synthase activity in the kidney and enhance renal sodium reabsorption, but it is unclear whether the increased citrate synthase activity is involved in renal sodium transport. We used the Wistar-Furth rat, an inbred strain found to be deficient in renal citrate synthase activity, as an experimental model to investigate this issue. We confirmed that renal citrate synthase activity from adrenalectomized Wistar-Furth rats was decreased compared with that from control Wistar rats (by 28%). Similarly, urinary citrate excretion was 23% lower in Wistar-Furth rats. Subnormal citrate formation in Wistar-Furth rats could not be accounted for by differences in systemic pH or circulating potassium levels. Because renal citrate synthase activity was reduced in Wistar-Furth rats, we hypothesized that renal sodium excretory responses to mineralocorticoids would be reduced as well. Four-hour sodium excretion after intraperitoneal injection of 5 microg of aldosterone was reduced by 56% in adrenalectomized Wistar rats and by 52% in adrenalectomized Wistar-Furth rats (both P<0.01 compared with vehicle injection). Similarly, the pattern of urinary sodium excretion in response to subcutaneous injections of deoxycorticosterone acetate over a 2-week period was similar in adrenalectomized Wistar and Wistar-Furth rats. In summary, acute and chronic antinatriuretic responses to mineralocorticoids are maintained in Wistar-Furth rats at the level of Wistar rats, despite the marked reduction in citrate synthase activity. These findings are not consistent with an important role for citrate synthase activity in mineralocorticoid-mediated renal sodium transport.

Adrenalectomy↗

PubMed1999

Using engineering and assistive technologies for rehabilitation after electrical trauma.

A framework is presented for judging when, how, and why rehabilitation engineering and its related assistive technologies are appropriate interventions following electrically induced trauma or burns. Instead of relying on the World Health Organization's medically based classification scheme of "Impairment, Disability, and Handicap," this newer framework is built on a rational demarcation proposed by the National Center for Medical Rehabilitation and Research at the U.S. National Institutes of Health. This latter client-centered framework encompasses pathophysiology, impairment, functional limitations, "disability", and societal limitations. This framework is well suited to handle the varied sequelae of electrical trauma and burn injuries and provides guidance towards the most effective use of traditional rehabilitation interventions and of assistive technologies. For electrical injuries, rehabilitative technologies can be classified as those promoting job accommodations (i.e., that help an individual return to active employment, albeit possibly in a different role) or as aids to the other activities of daily living (ADLs) that provide an enhanced quality of life to the individual with disability. While the traditional rehabilitative focus has been on return-to-work, especially among professional tradesmen, a more productive rehabilitative effort in some cases may occur through psychosocial adjustments achieved via effective technological interventions that enhance ADLs.

Accidents, Occupational↗

PubMed1999

Isometric torque about the knee joint generated by microstimulation of the cat L6 spinal cord.

Isometric torque was generated about the knee joint by microstimulation of the cat L6 spinal cord using a single microelectrode. The torque responses varied with microstimulation location. Appreciable extension torque was generated by microstimulation in ventrolateral locations of the L6 spinal cord. Stimulation parameters (intensity, frequency and pulse-width) also influenced the extension torque. Specific stimulation parameters (100 microA intensity, 40 Hz frequency and 0.20 ms pulse-width) appear best suited for mapping the spinal cord based on knee joint torque responses. Low levels of cocontraction of the extensor and flexor could be achieved when extension torque was produced, but also varied with the stimulation locations. There are locations in the L6 ventral horn where microstimulation could evoke sustained extension for at least 4 min with only a slight change in torque. This study suggests the possibility of restoring lower limb function in patients with spinal cord injury above the lumbar level.

Animals↗

PubMed1999

Knee elasticity influenced by joint angle and perturbation intensity.

The responses of the human knee joint system to small rotational displacements were studied in the horizontal plane to eliminate the effect of gravity. Band-limited noise was used to produce up to +/-3 degrees angular perturbations to the knee joint. Under these restricted conditions, the knee joint system could be described by a linear, second-order model with the assumption that the mechanical properties of the knee were constant over these small displacements. The elasticity about the knee was influenced not only by the static joint angle but also by the perturbation intensity. Realistic models of the knee joint system should be modeled by a position-dependent, nonlinear system to remain valid over a large range of rotation.

Adult↗

PubMed1999

Bioassays for growth factors.

Growth factors have a wide variety of actions in living systems, providing a range of potentially quantifiable responses for measurement of their biological activity. The biological activity has to be assessed by bioassay as it cannot be predicted from physicochemical data alone. Bioassay systems range from in vivo responses to changes in receptor binding and in early components of signal transduction pathways. The most commonly used systems are based on the measurement of responses of immortalized cell lines, which although not as functionally relevant as in vivo assays, are easier to use. Most growth factors have multiple actions on multiple targets, and can show differential changes in their different activities, so use of the biological activity measured in one bioassay system to predict biological activity in another system must be rigorously validated. Since the bioassay systems are themselves inherently variable, measurement of the growth factor's activity must be made relative to a common, stable, reference preparation to permit valid inter-assay and inter-laboratory comparisons.

Animals↗

PubMed1998

Design, control, and characterization of a Sliding Linear Investigative Platform for Analyzing Lower Limb Stability (SLIP-FALLS).

A novel device, the Sliding Linear Investigative Platform For Analyzing Lower Limb Stability (SLIP-FALLS), has been designed to study the detection and discrimination thresholds of humans to uniaxial horizontal step, ramp, or sinusoidal translations of the surface upon which they stand or stride. The device also can be used to test the human potential for, and mechanisms of, slips and falls. The SLIP utilizes air bearing technology and a noncontact linear motor to produce ultra-low-vibration translations. The FALLS system measures the forces on four load cells, platform linear and head tri-axial accelerations, four channels of electromyographic data, motor voltage, and a subject's psychophysical response; and derives other physiological and biomechanical measures, like center-of-pressure and shear force. The effect of acceleration and shear force on the accuracy of the center-of-pressure calculations is presented. Operating ranges depend on the interactions among displacement, velocity, acceleration, and jerk parameters for linear translations, and between amplitudes and frequencies for sinusoidal translations. Displacements from 5 microm to 0.277 m, velocities from 5 microm/s to 0.3 m/s, and accelerations up to 2.5 m/s2 are achievable with precise control (i.e., without overshoot), but tradeoffs exist such that all three maxima cannot be reached simultaneously. For a 0.15 m/s linear translation at 4 m/s2, SLIP-FALLS produces substantially less vibration than the worm-driven NeuroTest system. The usefulness of having precise control over movement parameters is discussed.

Biomechanical Phenomena↗

PubMed1998

The international standard for platelet-derived growth factor-BB: comparison of candidate preparations by in vitro bioassays and immunoassays.

In an international collaborative study, four preparations of recombinant, human sequence, platelet-derived growth factor-BB (PDGF-BB), two glycosylated and two nonglycosylated, were evaluated, using in vitro bioassays and immunoassays, by seven laboratories in three countries, for their suitability to serve as the international standard (IS) for PDGF-BB. The study shows that interlaboratory variation in estimates of PDGF-BB potency is reduced by use of a common standard. The bioassays, using various types of fibroblast, detected PDGF-BB and PDGF-AB as equally potent, while immunoassays discriminated between the two isoforms. On the basis of the results reported here, the World Health Organization (WHO) established the preparation coded 94/728 as the first IS for PDGF-BB, with an assigned unitage of 3000 International Units per ampoule. The IS may be obtained by writing to NIBSC, PO Box 1193, Potters Bar, EN6 3QH, UK, or through web site http:¿¿www.nibsc.ac.uk.

Becaplermin↗

PubMed1997

Murine strain differences in response to mercuric chloride: antinucleolar antibodies production does not correlate with renal immune complex deposition.

Mercuric chloride (HgCl2) induces the production of antinucleolar antibodies (ANucA) in susceptible strains of mice. Responder strains bearing the H-2(5) haplotype as well as several ANucA resistant strains have been shown to develop renal immune complex deposits after HgCl2 treatment. Sera obtained throughout 12 to 16 weeks of HgCl2 treatment from mice of four ANucA responder strains (A.SW/SnJ, A.CA/SnJ, DBA/1J, and P/J) and one ANucA-resistant strain (C57BL/10SnJ) were examined for ANucA production. Terminal sera were also tested for the presence of anti-glomerular basement membrane antibodies, and the kidneys were examined for the deposition of IgG and C3. Only one strain, A.SW, developed significant deposits of IgG in the renal glomeruli, although all four responder strains exhibited similar ANucA induction/production profiles. The differences seen by direct immunofluorescence assay (IFA) in renal immune complex deposition between the A.SW and histocompatibility congenic A.CA mice were corroborated by individually eluting and then quantitating the deposited IgG from renal tissues of Hg-treated A.SW and A.CA mice as well as control A.SW mice. The average amount of IgG eluted from A.SW renal tissue was significantly greater than that eluted from either A.CA or control A.SW renal tissues. All eluates from Hg-treated animals gave only a nucleolar fluorescence pattern when assayed by indirect IFA against a panel of rat organ tissues. In summary, no correlation was found between ANucA production and renal IgG deposition in response to treatment with HgCl2.

Animals↗

PubMed1997

Stress-activated protein kinases: activation, regulation and function.

The response of cells to extracellular stimuli is mediated in part by a number of intracellular kinase and phosphatase enzymes. Within this area of research the activation of the p42 and p44 isoforms of mitogen-activated protein (MAP) kinases have been extensively described and characterised as central components of the signal transduction pathways stimulated by both growth factors and G-protein-coupled receptor agonists. Signaling events mediated by these kinases are fundamental to cellular functions such as proliferation and differentiation. More recently, homologues of the p42 and p44 isoforms of MAP kinase have been described, namely the stress-activated protein kinases (SAPKs) or alternatively the c-jun N-terminal kinases (JNKs) and p38 MAP kinase (the mammalian homologue of yeast HOG1). These MAP kinase homologues are integral components of parallel MAP kinase cascades activated in response to a number of cellular stresses including inflammatory cytokines (e.g., Interleukin-1 (Il-1) and tumour necrosis factor-alpha (TNF-alpha), heat and chemical shock, bacterial endotoxin and ischaemia/cellular ATP depletion. Activation of these MAP kinase homologues mediates the transduction of extracellular signals to the nucleus and are pivotal events in the regulation of the transcription events that determine functional outcome in response to such stresses. In this review we highlight the identification and characterisation of the stress-activated MAP kinase homologues, their role as components of parallel MAP kinase pathways and the regulation of cellular responses following exposure to cellular stress.

Animals↗

PubMed1997

Testing peripheral somatosensory neuroprostheses by recording from raccoon cortex.

A topologically organized representation of the body surface exists within the mammalian somatosensory cortical areas such that stimulation of a part of the body surface will produce a response in a localized region of the contralateral somatosensory cortex. Because of this topography, we propose that the selectivity of a peripheral somatosensory neuroprosthetic electrode array can be tested by noting whether the locus of maximum activation in the cortex moves in a consistent manner when differing portions of the array are stimulated. We further propose that the raccoon might well be the ideal animal in which to test this hypothesis, since the raccoon has a rather unique cortical somatosensory area where each digit is represented in individual subgyri around the tri-radiate sulcus. To demonstrate the feasibility of this concept, a pilot study was carried out in one raccoon under barbiturate anesthesia. The median nerve was stimulated via selective quadrants of a nerve cuff array of four tripolar electrodes implanted around the nerve. Cuff stimulation produced short-latency evoked surface potentials in the digit areas of the raccoon first somatosensory cortex. Response selectivity could be demonstrated, as could a separation between thresholds for producing movement or producing cortical evoked potentials. The sensory and motor responses elicited were consistent with the orientation of the median nerve within the cuff as determined by a postmortem identification of the muscle innervation pattern of the nerve.

Animals↗

PubMed1997

Resistance to mineralocorticoids in Wistar-Furth rats.

Wistar-Furth rats (WF) do not develop hypertension when treated with salt and mineralocorticoids and therefore may be useful for investigating the mechanisms of mineralocorticoid action and hypertension. In the present studies, we determined vascular and renal responses of WF to mineralocorticoids. Control Wistar rats (W) developed deoxycorticosterone acetate (DOCA)-NaCl and dexamethasone hypertension, whereas WF rats developed dexamethasone hypertension only. Aldosterone treatment of vascular smooth muscle cells cultured from WF resulted in 82% less upregulation of angiotensin II radioligand binding, 50% less induction of angiotensin II AT1a receptor mRNA, and 76% less potentiation of angiotensin II-stimulated inositol phosphates than did aldosterone treatment of cells from W. Similarly, DOCA-NaCl potentiated angiotensin II- and phenylephrine-stimulated contractions in aortic rings from W but not from WF. Although DOCA-NaCl treatment affected hypokalemia to an equal degree in WF and W, increases in renal citrate synthase activity (a specific renal mineralocorticoid response) were greater in W than in WF. WF manifest a partial defect in mineralocorticoid responsiveness in vascular smooth muscle and, possibly, in the kidney.

Aldosterone↗

PubMed1996

Treatment of vascular smooth muscle cells with antisense phosphorothioate oligodeoxynucleotides directed against p42 and p44 mitogen-activated protein kinases abolishes DNA synthesis in response to platelet-derived growth factor.

We have investigated the requirement for mitogen-activated protein (MAP) kinase in the stimulation of DNA synthesis by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells using a phosphorothioate-modified oligodeoxy-nucleotide (ODN) to deplete MAP kinase. Treatment for 72 h with MAP kinase antisense ODN directed against both the p42 and p44 isoforms of MAP kinase abolished the expression of MAP kinase and reduced agonist-stimulated MAP kinase activity by approx. 95%. The scrambled control ODN was without effect, but the sense control ODN slightly enhanced the expression of both isoforms. Abolition of MAP kinase activity by antisense ODN treatment prevented angiotensin II- and PDGF-stimulated activation of p90 ribosomal S6 kinase activity, but did not affect activation of MAP kinase kinase. In addition, antisense ODN pretreatment reduced PDGF-stimulated [3H]thymidine incorporation to < 5% of control, and decreased basal incorporation by approx. 90%. In contrast, basal [3H]thymidine incorporation was enhanced approx. 60% by control sense ODN treatment. These results indicate an obligatory role for MAP kinase in the activation of a number of early events in mitogenesis, including DNA synthesis, in vascular smooth muscle cells.

Animals↗

PubMed1996

Efficacy of agonist-stimulated MEK activation determines the susceptibility of mitogen-activated protein (MAP) kinase to inhibition in rat aortic smooth muscle cells.

In rat aortic smooth muscle cells, platelet-derived growth factor (PDGF) stimulated a sustained activation of mitogen-activated protein kinase (MAP kinase) while the response to angiotensin II (AII) was transient. This was due to a relatively greater initial activation of MAP kinase kinase (MEK) and a correspondingly greater residual MEK activity at later time points. Pretreatment of cells with the novel MEK inhibitor PD 098059 reduced MEK activation at 5 min in response to each agonist by a similar proportion (70%); however, at this time point MAP kinase activation in response to PDGF was only marginally affected while the response to AII was substantially reduced. PD 098059 did, however, reduce PDGF-stimulated MEK activity after 30 min and this correlated with a loss in MAP kinase activity and DNA synthesis. Pretreatment with forskolin also caused a similar pattern of inhibition of agonist-stimulated MEK and MAP kinase activity. Only following protein kinase C down-regulation were both AII- and PDGF-stimulated MAP kinase activation substantially reduced and this correlated with the virtual loss of both MEK and c-Raf-1 activity in response to both agents. The differential inhibition of MAP kinase activation by forskolin was not due to specific activation of A-Raf by PDGF; both PDGF and AII stimulated A-Raf kinase and this activity was strongly inhibited by forskolin. These results suggest that the efficacy of MEK activation determines the duration of MAP kinase activation and the susceptibility of MAP kinase activation to inhibition by different agents. The results also argue against the selective activation of A-Raf by PDGF as a mechanism to explain the differences in the kinetics of MAP kinase activity stimulated by AII and PDGF.

Angiotensin II↗

PubMed1996

The raccoon as an animal model for upper limb neural prosthetics.

The raccoon was evaluated as an animal model for upper limb neural prosthetics. This animal was selected primarily because the functional use of its forelimb mimics in many ways the usage in humans and because of its optimal size and commercial availability. Eight cadaver and fresh specimen forearms were dissected. Important characteristics of the raccoon forearm were: 1) large muscles in the volar forearm, 2) large digits in the paw that appear more similar to humans than to other species such as cat or dog, 3) persistence of two median nerve cords into the forearm, 4) no separation of individual tendons of flexor digitorum superficialis and flexor digitorum profundus in the carpal tunnel, 5) a small thumb digit with little function and 6) a primary origin of flexor policis longus on the proximal ulna with a secondary origin on the radius. Four animals were anesthetized and responses of the forearm and paw to stimulation of the volar forearm muscles with percutaneous electrodes were evaluated. A pair of stimulating electrodes was placed in each of four muscles or muscle groups. Recording electrodes were placed in two muscles which showed the greatest separation of muscle movements to stimulation. Stimulation currents just above threshold produced discrete motion as well as recordable EMG M-waves. Incremental increases in stimulation current produced an increase in M-wave amplitude up to a maximal stimulating current. Torque recordings for pronation, wrist flexion and finger flexion showed graded and selective responses. These results including anatomical descriptions indicate both the limitations of this animal model and its potential use in the development of upper limb neural prosthetics. We conclude that the raccoon model may be superior to other nonprimate animal models such as the cat because of its extensive forearm and paw movements.

Animals↗

PubMed1996

The international standard for epidermal growth factor (EGF): comparison of candidate preparations by in vitro bioassays and immunoassays. National Institute for Biological Standards and Control.

Four preparations of recombinant human sequence epidermal growth factor (EGF), two of the full length 53-amino acid chain, and two of the 52-amino acid chain, lacking the carboxyl-terminal arginine, were evaluated, using a variety of in vitro bioassays and immunoassays, by 12 laboratories in seven countries, for their suitability to serve as the international standard for EGF. The study shows that some assay systems appear to discriminate between the full length and the 52-amino acid forms of EGF and that use of a common standard in place of the various in-house standards leads to a substantial decrease in between-laboratory variances in estimates of potency of EGF samples. On the basis of the results reported here, the World Health Organization (WHO) established one of the preparations of the full-length EGF molecule (coded 91/530) as the first international standard (IS) for EGF, with an assigned unitage of 2000 International Units/ampoule, and one of the preparations of EGF(1-52) (coded 91/550) as the first international reference reagent (IRR) for EGF (1-52) with a nominal mass content of 1.75 microg EGF(1-52)/ampoule. The IS for EGF and the IRR for EGF(1-52) may be obtained by writing to NIBSC, PO Box 1193, Potters Bar, EN6 3QH, UK.

Biological Assay↗

PubMed1995

Circulating human factor IX produced in keratin-promoter transgenic mice: a feasibility study for gene therapy of haemophilia B.

It has previously been suggested that keratinocytes might provide a suitable target cell for delivery of factor IX to the systemic circulation for gene therapy of haemophilia B. Here, an investigation of the use of cellular gene promoters specific for keratinocytes was undertaken to examine whether factor IX could be passed from the epidermis to the systemic circulation. Utilizing two bovine cytokeratin gene promoters, BKIII and BKVI, three lines of transgenic mice were generated with targeted expression of human factor IX in the epidermis. All three transgenic mouse lines secreted epidermally derived human factor IX into the blood system. Most effective factor IX expression (46 ng/ml steady-state levels of circulating human factor IX) was obtained utilizing the BKVI gene promoter, the human homologue of K10, which is expressed exclusively in differentiated keratinocytes, localized distal to the basement membrane. This report demonstrates, for the first time, that human factor IX can be efficiently synthesized and secreted from keratinocytes in situ, and can cross the epidermal basement membrane to reach the systemic circulation. The transgenic mouse model will provide a good in vivo system with which to optimize the efficiency of different keratin gene promoter constructs for delivery of therapeutic gene products to the serum, especially for those promoters, such as K10, which are not effectively expressed in vitro.

Animals↗

PubMed1994

Biomechanical and reflex responses to joint perturbations during electrical stimulation of muscle: instrumentation and measurement techniques.

A test device is developed to measure ankle joint compliance and muscle activity when the ankle is subjected to perturbations in angular position (or torque) from bias positions achieved volitionally or via electrical stimulation. The ankle measurement system uses a pivoting footplate and is operable with the subject sitting or supine. A companion platform for the knee is developed that uses a rotary arm and attached leg brace and is operable with the subject's leg in the horizontal or vertical plane. The knee fixture's pivoting arm can slide to account for the cam-like movement of the knee during rotation. The devices use similar hardware and share common instrumentation and control. Precise torque or position perturbations are delivered by a computer-controlled torque motor to the ankle or knee. Angular displacement, torque, acceleration, knee fixture moment arm and electromyographic data are collected on analogue tape and simultaneously digitised and stored. A special stimulator/recording amplifier permits the recording of electromyographic signals from the stimulated muscle. Experimental data indicate that the ankle and knee devices, operated horizontally, are purely inertial systems. Sample ankle and knee joint responses to perturbations are presented.

Ankle Joint↗