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Biomedical subjects

G A Robertson

Publications and source records attributed to G A Robertson.

At least 19 recordsLinked to original sources
PubMed1998

Properties of HERG channels stably expressed in HEK 293 cells studied at physiological temperature.

We have established stably transfected HEK 293 cell lines expressing high levels of functional human ether-a go-go-related gene (HERG) channels. We used these cells to study biochemical characteristics of HERG protein, and to study electrophysiological and pharmacological properties of HERG channel current at 35 degrees C. HERG-transfected cells expressed an mRNA band at 4.0 kb. Western blot analysis showed two protein bands (155 and 135 kDa) slightly larger than the predicted molecular mass (127 kDa). Treatment with N-glycosidase F converted both bands to smaller molecular mass, suggesting that both are glycosylated, but at different levels. HERG current activated at voltages positive to -50 mV, maximum current was reached with depolarizing steps to -10 mV, and the current amplitude declined at more positive voltages, similar to HERG channel current expressed in other heterologous systems. Current density at 35 degrees C, compared with 23 degrees C, was increased by more than twofold to a maximum of 53.4 +/- 6.5 pA/pF. Activation, inactivation, recovery from inactivation, and deactivation kinetics were rapid at 35 degrees C, and more closely resemble values reported for the rapidly activating delayed rectifier K+ current (I(Kr)) at physiological temperatures. HERG channels were highly selective for K+. When we used an action potential clamp technique, HERG current activation began shortly after the upstroke of the action potential waveform. HERG current increased during repolarization to reach a maximum amplitude during phases 2 and 3 of the cardiac action potential. HERG contributed current throughout the return of the membrane to the resting potential, and deactivation of HERG current could participate in phase 4 depolarization. HERG current was blocked by low concentrations of E-4031 (IC50 7.7 nM), a value close to that reported for I(Kr) in native cardiac myocytes. Our data support the postulate that HERG encodes a major constituent of I(Kr) and suggest that at physiological temperatures HERG contributes current throughout most of the action potential and into the postrepolarization period.

Action Potentials↗
PubMed1997

Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current.

HERG, the human ether-a-go-go-related gene, encodes a K(+)-selective channel with properties similar to the rapidly activating component of the delayed rectifier K+ current (IKr). Mutations of HERG cause the autosomal-dominant long-QT syndrome (LQTS), presumably by disrupting the normal function of IKr. The current produced by HERG is not identical to IKr, however, and the mechanism by which HERG mutations cause LQTS remains uncertain. To better define the role of Erg in the heart, we cloned Merg1 from mouse genomic and cardiac cDNA libraries. Merg1 has 16 exons and maps to mouse chromosome 5 in an area syntenic to human chromosome 7q, the map locus of HERG. We isolated three cardiac isoforms of Merg1: Merg1a is homologous to HERG and is expressed in heart, brain, and testes, Merg1a' lacks the first 59 amino acids of Merg1a and is not expressed abundantly, and Merg1b has a markedly shorter divergent N-terminal cytoplasmic domain and is expressed specifically in the heart. The Merg1 isoforms, like HERG, produce inwardly rectifying E-4031-sensitive currents when heterologously expressed in Xenopus oocytes. Merg1a and HERG produce currents with slow deactivation kinetics, whereas Merg1a' and Merg1b currents deactivate more rapidly. Merg1b coassembles with Merg1a to form channels with deactivation kinetics that are more rapid than those of Merg1a or HERG and nearly identical to IKr. In addition, a homologue of Merg1b is present in human cardiac and smooth muscle. Thus, we have identified a novel N-terminal Erg isoform that is expressed specifically in the heart, has rapid deactivation kinetics, and coassembles with the longer isoform in Xenopus oocytes. This N-terminal Erg isoform may determine the properties of IKr and contribute to the pathogenesis of LQTS.

Amino Acid Sequence↗
PubMed1996

Potassium currents expressed from Drosophila and mouse eag cDNAs in Xenopus oocytes.

The ether-a-go-go (eag) gene family encodes a set of related ion channel polypeptides expressed in the excitable cells of organisms ranging from invertebrates to mammals. Earlier studies demonstrated that eag mutations in Drosophila cause an increase in membrane excitability in the nervous system. Mutations in the human eag-related gene (HERG) have been implicated in cardiac arrhythmia, and recent studies show that HERG subunits contribute to the channels mediating IKr and the terminal repolarization of the cardiac action potential. A physiological role for M-EAG, the mouse counterpart to Drosophila eag, has not been determined. Here, we describe basic properties of Eag and M-EAG channels expressed in frog oocytes, using two-electrode voltage clamp and patch clamp techniques. Both Eag and M-EAG channels are voltage-dependent, outwardly rectifying and highly selective for K+ over Na+ over Na+ ions. In contrast to previous reports, we found no evidence for Ca2+ flux through Eag channels. The most notable difference between these closely related channels is that Eag currents exhibit partial inactivation, whereas M-EAG currents are sustained for the duration of an activating voltage command. In addition, Eag currents run down more rapidly than do M-EAG currents in excised macropatches. Rundown is reversible by inserting the patch into the interior of the oocyte, indicating that a cytosolic factor regulates channel activity or stability. These studies should facilitate identification of currents mediated by Eag and M-EAG channels in vivo.

Animals↗
PubMed1995

HERG, a human inward rectifier in the voltage-gated potassium channel family.

In contrast to other members of the Eag family of voltage-gated, outwardly rectifying potassium channels, the human eag-related gene (HERG) has now been shown to encode an inwardly rectifying potassium channel. The properties of HERG channels are consistent with the gating properties of Eag-related and other outwardly rectifying, S4-containing potassium channels, but with the addition of an inactivation mechanism that attenuates potassium efflux during depolarization. Because mutations in HERG cause a form of long-QT syndrome, these properties of HERG channel function may be critical to the maintenance of normal cardiac rhythmicity.

Animals↗
PubMed1995

Intra- and interexaminer reliability of the chiropractic biophysics lateral lumbar radiographic mensuration procedure.

OBJECTIVE: To determine the intra- and interexaminer reliability of a specific method of mensuration commonly used to evaluate the positional configuration of the lumbopelvic spine viewed on lateral lumbar radiographs. DESIGN: A blind, repeated-measures design was used. Lateral lumbopelvic radiographs were presented to each of three examiners in random order. Each film was marked and measurements were recorded. The films were cleaned of all markings and randomized again for a second run by each examiner. Each examiner's measurements were unavailable to the other examiners. SETTING: Private, primary-care chiropractic clinic. MAIN OUTCOME MEASURES: Anterior/posterior thoracic translation in millimeters, Ferguson's sacral-plane angle to horizontal, arcuate line angle to horizontal, L1 to L5 absolute rotation angle and four relative rotation angles for L1-L2, L2-L3, L3-L4 and L4-L5. Intra- and interrelibility of the three radiographic examiners were analyzed. RESULTS: Intraexaminer reliability for (a) L1-L5 absolute rotation angle was .98, with confidence intervals included in the range of 0.95-0.99, (b) anterior/posterior thorax translation [+/- Sz] was .97-.99, with confidence intervals included in the range of 0.94-1.00, (c) arcuate angle (AA) .40-.81, with confidence intervals included in the range of 0.07-0.90, (d) Ferguson's angle (FA) was .91-.97, with confidence intervals included in the range of 0.82-0.98, (e) relative rotation angle reliability ranges were L1-L2, .84-.94; L2-L3, .80-.85; L3-L4, .78-.89; L4-L5, .87-.92. Interexaminer reliabilities for the three examiners ranged from .66-.98. CONCLUSION: With the exception of the arcuate angle measurement, the reliabilities for all other measurements were at least .78. Those measurements with reliabilities approaching .80 or better would be considered accurate enough for use in future clinical studies. The arcuate angle measurement may have been least reliable because of the subjective nature of the method of affixing a best-fit line to a radiographic landmark that often takes on the appearance of a mild curvature. Establishing reliability is an important first step toward evaluating these and other similar radiographic measurements that have yet to be examined for their validity.

Analysis of Variance↗
PubMed1993

Entrapment neuropathy of the palmar cutaneous nerve within its tunnel.

A case of isolated entrapment of the palmar cutaneous branch of the median nerve is presented. At operation, a ganglion compressing the nerve within its tunnel was found. Symptoms were relieved with no recurrence at 2 years after decompression and excision of the ganglion.

Carpal Tunnel Syndrome↗
PubMed1993

An anatomical study of the deep transverse metacarpal ligament.

The anatomy of the deep transverse metacarpal ligament was examined in cadaveric dissections. Previously unreported findings were transverse muscular slips from abductor digiti minimi that inserted into the medial border of the ligament and, in 1 case, an extension from the medial half of the tendon of extensor carpi ulnaris that inserted into the medial aspect of the ligament. Applied anatomy in relation to the dynamics of the transverse metacarpal arch is reviewed.

Finger Joint↗
PubMed1992

A biomechanical analysis of a new interlock suture technique for flexor tendon repair.

Using a computerised tensometer, both the gap-producing and breaking forces of a new interlocking suture for flexor tendon repair were compared to the modified Kessler and the Strickland techniques. 30 porcine deep flexor tendons were used in each group and all repairs were performed with 3/0 polypropylene sutures. The interlock technique withstood gap-producing and breaking forces significantly better than the modified Kessler and Strickland techniques. Also, the gap-producing force was closer to the breaking force with the interlock technique than with the other two techniques.

Animals↗
PubMed1991

A component of calcium-activated potassium channels encoded by the Drosophila slo locus.

Calcium-activated potassium channels mediate many biologically important functions in electrically excitable cells. Despite recent progress in the molecular analysis of voltage-activated K+ channels, Ca(2+)-activated K+ channels have not been similarly characterized. The Drosophila slowpoke (slo) locus, mutations of which specifically abolish a Ca(2+)-activated K+ current in muscles and neurons, provides an opportunity for molecular characterization of these channels. Genomic and complementary DNA clones from the slo locus were isolated and sequenced. The polypeptide predicted by slo is similar to voltage-activated K+ channel polypeptides in discrete domains known to be essential for function. Thus, these results indicate that slo encodes a structural component of Ca(2+)-activated K+ channels.

Amino Acid Sequence↗
PubMed1991

Iliac-enteric fistula following Dacron patch angioplasty.

We report a patient who developed fistulization between the jejunum and a Dacron patch placed at the bifurcation of the right common iliac artery during endarterectomy 14 years previously. The patient was successfully managed by resection of the iliac bifurcation and a segment of the involved bowel. While arterio-enteric fistulae typically involve prosthetic grafts, they may occur in association with artificial materials used to patch endarterectomy sites; hence, knowledge of technical detail is important in the diagnosis of this complication following endarterectomy.

Aged↗
PubMed1991

Acquired nostril stenosis.

Acquired nostril stenosis is an uncommon but challenging problem. Etiology, pathophysiology, presentation, and treatment options are presented, together with two patient reports. A classification is offered that allows for appropriate selection of the surgical procedure.

Child↗
PubMed1988

A microtiter cell-culture assay for the determination of anti-human immunodeficiency virus neutralizing antibody activity.

A microtiter cell-culture assay is described for measuring neutralizing antibody activity directed against the human immunodeficiency virus (HIV). The assay relies upon inhibition of HIV-mediated cell killing of infected MT-4 lymphoid cells. The assay exhibits comparable sensitivity to two other methods used for such measurements, is relatively rapid, may be adapted for screening large numbers of samples and involves minimal handling of infectious virus.

Antibodies, Viral↗
PubMed1988

Synaptic control of hindlimb motoneurones during three forms of the fictive scratch reflex in the turtle.

1. The turtle spinal cord produces three forms of the fictive scratch reflex in response to tactile stimulation of sites on the body surface. Common to all three forms is the rhythmic alternation of activity between hip protractor and hip retractor motoneurones. Hip protractor motoneurone activity is monitored via nerves innervating the hip protractor muscle puboischiofemoralis internus pars anteroventralis (VP-HP). Hip retractor activity is monitored via nerves innervating several monoarticular hip retractor muscles, one hip adductor muscle, and several biarticular hip retractor-knee flexor muscles (HR-KF). Each form is characterized by the timing of activity of motoneurones innervating femorotibialis (FT-KE), a monoarticular knee extensor muscle, within this alternating cycle (Robertson, Mortin, Keifer & Stein, 1985). In the present study, intracellular recordings revealed a corresponding regulation of synaptic drive to knee extensor motoneurones with respect to the synaptic drive to the motoneurones innervating antagonist muscles of the hip. These patterns of synaptic activation give rise to the distinct motor pattern underlying each form of the scratch reflex. 2. VP-HP, HR-KF and FT-KE motoneurones all exhibited phasic depolarizing and hyperpolarizing changes in membrane voltage during the production of the rhythmic motor patterns underlying each stratch form. Membrane depolarization is caused by synaptic excitation (EPSPs) and gives rise to motoneurone discharge. Hyperpolarization is primarily the result of postsynaptic inhibition (IPSPs) mediated by an increased conductance of chloride ions (Cl-) and ensures motor pool quiescence during antagonist activation. 3. VP-HP motoneurones depolarized during activation of the VP-HP motor pool and hyperpolarized during activation of the HR-KF motor pool. HR-KF motoneurones depolarized during activation of the HR-KF motor pool and hyperpolarized during activation of the VP-HP motor pool. In many cases, the amplitude of hyperpolarization was directly related to the intensity of the antagonist motor pool burst. During the rostral scratch, HR-KF motor pool activity was sometimes deleted, along with the depolarizing wave in HR-KF motoneurones and the hyperpolarizing wave in VP-HP motoneurones. The interneurones providing the synaptic drive to these antagonist motoneurones appear, therefore, to have reciprocal activation patterns. 4. FT-KE motoneurones depolarized during FT-KE motor pool activation and hyperpolarized during FT-KE motor pool quiescence. This alternation of opposing synaptic drive underlies the rhythmic activation of the FT-KE motor pool during all scratch forms.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

The role of sternum in osteomyocutaneous reconstruction of major mandibular defects.

Replacement of skeletal support after extensive intraoral resection demands the use of a vascularized bone graft. This can be provided by microvascular free transfer using the ilium or metatarsal bones or by using muscle as a vascular carrier, employing the rib, the spine of the scapula, or the clavicle. Over a 5 year period, 27 patients underwent mandibular reconstruction with a vascularized segment of the outer table of sternum transposed together with a skin island on the pectoralis major muscle. Loss of bone occurred in two patients. A 93 percent survival rate was achieved. An earlier, smaller series of six patients using rib for reconstruction resulted in an unacceptably high complication rate. Success in survival of the bone graft, however, is not enough to procure a satisfactory result. Specific aspects of surgical technique are described that create an alveolar ridge with a sulcus on either side that can accept a denture; a diaphragm to replace the floor of the mouth and eliminate dead space; and an esthetically acceptable appearance, with definition of the jawline and a properly supported lower lip.

Adult↗
PubMed1986

A comparison between sternum and rib in osteomyocutaneous reconstruction of major mandibular defects.

Following major mandibular resection for intraoral malignancy, 6 patients underwent reconstruction using rib and 22 patients underwent reconstruction using the outer table of the sternum; the pectoralis major muscle was used as the vascular carrier for both bone and skin in all patients. Five of the 6 patients in the rib group encountered major complications. In the sternal group, loss of bone occurred in only 2 of 22 patients. Those aspects of technique considered important to the outcome are detailed. Results are discussed in terms of bone survival, intraoral features including denture placement, and the patient's appearance. The sternal transfer has consistently shown itself to be superior to rib, in terms of both early morbidity and later functional and aesthetic results. It is our present method of choice for reconstruction following major intraoral resection.

Bone Transplantation↗