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Biomedical subjects

G Gordon

Publications and source records attributed to G Gordon.

At least 91 records · Page 5Linked to original sources

The use of retrograde transport of horseradish peroxidase for studying the dendritic trees and axonal courses of particular groups of tract cells in the spinal cord.

Modifications have been made in Mesulam 's method for labelling neurons by retrograde transport of horseradish peroxidase, with tetramethylbenzidine as chromogen, with the object of increasing the extent of labelling of dendrites and axons. A procedure was devised specifically for studying spinomedullary and medullospinal tract systems, involving implanting easily-made HRP-agar pellets into areas of controlled damage in particular spinal fascicles, and sealing the site of implant with cyanoacrylate glue. Lesions of other fascicles were often made to limit transport to the implanted fascicle. Fourth-order dendrites were regularly labelled over long (30 cm or more) transport distances: axons were also labelled over this whole distance, often allowing exact study of the initial course of particular axons. Controls in both cat and rat showed that the uptake of HRP under these circumstances occurred almost wholly from the region of axonal damage at the site of implant which can be characterized histologically.

Animals↗

Spinally projecting neurons in the dorsal column nuclei: distribution, dendritic trees and axonal projections. A retrograde HRP study in the cat.

The distribution, dendritic trees and axonal courses of spinally projecting cells in the dorsal column nuclei were studied after labelling by retrograde HRP transport. The region of densest distribution was at the base of the two nuclei and in the area between them, extending for about 2 mm caudally from the obex. Only very few cells were found inside the cell cluster regions of the nuclei, where their dendrites had a free stellate form. The great majority, lying between, deep, or rostral to the cluster regions, also had a stellate form, except where they impinged on the boundaries of the cluster regions or on other nuclear borders; the spread of dendrites was dramatically restricted at such boundaries, often leading to a fusiform appearance in transverse sections which however was not evident in the parasagittal plane. No justification was therefore found for subdividing the population on morphological grounds. Axons of these cells descended ipsilaterally in either the medial part of the dorsolateral fascicle or in the adjacent lateral part of the cuneate fascicle, at cervical levels, and probably in about equal numbers. Most axons destined for the DLF followed a deep caudolateral trajectory, while many destined for the DC had a more dorsal or lateral course. Collateral branches were seen within the nuclei but could not be followed far. The fact that few if any cells lying in the region of maximum distribution of the spinally projecting cells were labelled following injections of HRP into the thalamic ventroposterior nucleus emphasizes that they form a distinctive entity within this medullary nuclear complex, and that any axon branches they give into the contralateral brainstem must have some other destination than the VPL. Two other groups of neurons were labelled by HRP implants into the dorsal columns - one in the ventrolateral medullary reticular formation, and the other in the nucleus of the solitary tract.

Afferent Pathways↗

Sequence of the regulatory region of omp T, the gene specifying major outer membrane protein a (3b) of Escherichia coli K-12: implications for regulation and processing.

The DNA of the promoter region of omp T, including the putative start for the pro-Omp T protein (pro-protein a), has been sequenced. Previous studies showed that trypsin inhibitors prevent the processing of pro-Omp T to Omp T protein which led to the prediction that the processing site would be a lysine or an arginine. The deduced amino acid sequence contains a lysine at amino acid 12 and an arginine at amino acid 17 from the N terminus. Chou-Fassman analysis would predict processing at the lysine (but not the arginine) to remove a 1389 dalton peptide, consistent with the fact that the estimated molecular masses of pro-Omp T and Omp T are 42 kd and 40 kd respectively. In addition, the predicted mRNA of the promoter region can form a stable secondary structure (-17.1 kcal) that sequesters the Shine-Dalgarno (SD) sequence as well as the initiator AUG codon. There is evidence that the per A (tpo, envZ) gene product is required for synthesis of Omp T protein (as well as several outer membrane and periplasmic proteins). The perA gene product could be activating translation of Omp T protein by disrupting the mRNA secondary structure that sequesters the SD sequence. Omp T protein synthesis is reduced at temperatures below 32 degrees C and this may also be related to the greater stability of the sequestered SD sequence of the mRNA at low temperature.

Bacterial Outer Membrane Proteins↗

Antagonism of the effects of midazolam on phrenic nerve activity in the dog by Ro 15-1788 and Ro 15-3505.

Experiments were performed on 14 anaesthetized, artifically ventilated dogs, in which efferent activity in the phrenic nerve was recorded and blood-gas tensions, arterial pH and core temperature were controlled. Doses of midazolam between 0.2 mg kg-1 and 2 mg kg-1 abolished phrenic nerve activity for periods between 30 and 90 min. Ro 15-1788 in doses between 0.06 mg kg-1 and 1 mg kg-1 and Ro 15-3505 0.2-2 mg kg-1 reversed the effects of midazolam on phrenic nerve activity. Prior administration of these drugs either abolished or greatly inhibited the action of midazolam. When the preparations were observed for up to 2 h, there was no evidence of return of the action of midazolam, suggesting that both antagonists had a duration of action at least as long as that of midazolam.

Action Potentials↗

Effect of halothane on lymph flow.

The thoracic lymph duct was cannulated at the root of the neck in seven anaesthetized, artificially ventilated dogs. The mean control lymph flow was 1.51 ml kg-1 h-1 (SD +/- 0.35). The administration of 1% halothane caused a 59% decrease in mean lymph flow (to 0.62 ml kg-1 h-1) within 20 min, which returned to control values 30 min after the discontinuation of the administration of halothane.

Animals↗

Dental sequelae to the binge-purge syndrome (bulimia): report of cases.

The "thin-is-in" syndrome that obsesses many young people today leads to many severe medical and dental complications. Dental damage that follows the binge-purge episodes is reduced by strict management of oral hygiene; the damage is not totally correctable until the habit is well controlled through proper psychotherapy.

Adolescent↗

Thyroid gland pigmentation and minocycline therapy.

Thyroid pigments in black thyroid glands from minocycline-treated patients were compared by light and electron microscopy, histochemistry, and energy-dispersive x-ray analysis with minocycline-induced pigment in thyroid glands of laboratory animals, and with naturally occurring lipofuscins in untreated laboratory animals and humans. All thyroid samples examined contained nonbirefringent, Schmorl-positive pigment. However, the pigments in black thyroids from minocycline-treated patients resembled lipofuscins of untreated humans since both fluoresced and were Ziehl-Neelsen- and Sudan IV-positive. Minocycline induced pigment in rats was nonfluorescent and Ziehl-Neelsen- and Sudan IV-negative. Ultrastructurally, pigments in black thyroid glands of minocycline-treated humans resembled lipofuscins in untreated humans, and initial elemental analyses yielded similar spectra. Repeated analyses of the most electron-dense pigment deposits yielded spectra that resembled those of minocycline-induced pigment in laboratory animals-ie, both contained calcium. Black thyroid glands associated with minocycline administration contained predominantly lipofuscins with a small amount of another, possibly minocycline-related pigment. The absence of functional changes in patients and animals given minocycline suggests that discoloration of the thyroid gland associated with minocycline administration is innocuous. This is further supported by the lack of documented changes in thyroid physiology in patients that have received tetracyclines for a variety of indications in the last 30-odd years since their introduction to therapy.

Adult↗

Timing of corticofugal actions on the gracile and cuneate nuclei of the cat.

A comparison is presented of the latencies of corticofugal effects from the contralateral somatosensory cortex (SI) onto the cat's dorsal column nuclei (d.c.n.) under pentobarbitone anaesthesia. The latencies for transmission in the ascending pathway from d.c.n. to SI after stimulation within the gracile and cuneate nuclei were found to be 3.3 ms for the former and 2.8 ms for the latter. The time courses of inhibition of a medial lemniscal mass response following cortical conditioning and evoked by stimulation of peripheral nerves were measured. All latencies were corrected to exclude the different times taken for stimuli to reach the nuclei from the two limbs. The optimal condition-test interval was 12 ms with a duration of 14.3 ms for the superficial radial nerve (s.r.n.) and 45 ms and 30 ms respectively for the medial plantar nerve (m.p.n.). In each case cortical conditioning inhibited the wave by about 50%. The effect of cortical conditioning upon spontaneously firing d.c.n. single units was investigated. For cuneate cells the mean latency was 6.8 ms and the mean duration 36.8 ms. For gracile cells the latency of onset of inhibition was 17.2 ms and its duration 129 ms. In 75% of cells mixed effects were seen with facilitation preceding inhibition. The latencies of 'corticofugal reflex' action on the gracile and cuneate nuclei after stimulation of the s.r.n. and m.p.n. were determined. The gracile response had a latency approximately 4 times that for the cuneate response. The temporal asymmetry of these corticofugal effects suggests that the pathway is not purely a simple feed-back loop, but may be concerned in other physiological contexts, some of which are discussed.

Animals↗

omp T: Escherichia coli K-12 structural gene for protein a (3b).

Chromosomal DNA from strain UT400, a previously described deletion mutant of Escherichia coli K-12 that lacks outer membrane protein a, failed to hybridize with plasmid DNA (pGGC110) containing the structural gene for protein a. We designate the genetic locus for protein a, located at approximately 12.5 min of the E. coli chromosome, ompT.

Bacterial Outer Membrane Proteins↗

Dorsolateral spinal afferents to some medullary sensory nuclei. An anatomical study in the cat.

The course and termination of afferents in the spinal dorsolateral fascicle to some medullary sensory nuclei were studied by tracing degeneration following lesions of spinal white matter. The main conclusions depend on successive degeneration experiments; other points were studied with single-stage lesions. The dorsal column nuclei were particularly studied; terminations in these nuclei following dorsolateral lesions followed a clear-cut pattern, with fibres arising from segments below T6 terminating in the gracile nucleus and those with more rostral origin solely in the cuneate nucleus. In both nuclei, the major terminations were in their rostral third with most fibres traversing deep caudal regions where some termination also occurred. Some fibres ended contralaterally. These restricted regions of termination contrasted with the wide-spread terminations seen after lesions of the dorsal column. A region at the cuneate rostral pole, adjacent to but clearly separable from nucleus z, receives a dense projection from both caudal and rostral spinal levels, the former fibres terminating in the dorsal part of the region, the latter extending more ventrally. We treat this as a separate subnucleus. The afferents to the dorsal column (together with those terminating in the other nuclei studied) were confined to the extreme dorsolateral white matter. Our observations confirm the established view that only afferents arising from caudal segments (below at least T 4-5) terminate in nucleus z, and that afferents terminating in group x arise from all levels (at least between C5 and L5): also that neither receives any afferents through the dorsal columns. Dorsolateral fibres arising from segments above at least T6 terminate in a clear-cut area at the lateral border of the external cuneate nucleus. Heavy terminal degeneration was also seen in the lateral cervical nucleus of afferents arising from both above and below T 4-5.

Afferent Pathways↗

Remote monitoring by mass spectrometry during anaesthesia. Evaluation of a suitable inlet system.

We describe a three-stage mass spectrometer inlet system suitable for use in operating theatres and evidence of its performance in delay and response times to step changes in oxygen and halothane concentrations. At 55 m and a sampled gas flow of 100mlmin-1, the inlet imposed a delay of 21s and prolonged the 10-90% response to 310ms for oxygen and 510ms for halothane. A linear relationship between inlet length and 10-90% response time at constant sampled gas flow was demonstrated for halothane but not for oxygen. Our results compared with those of other workers support the chosen compromise between practical flexibility and convenience versus maximum speed of response that was adopted in this system design.

Anesthesia, Inhalation↗

Safety assessment of new anticancer compound, mitoxantrone, in beagle dogs: comparison with doxorubicin. II. Histologic and ultrastructural pathology.

Beagle dogs received either doxorubicin hydrochloride (1.75 mg/kg) or mitoxantrone (0.125 or 0.25 mg/kg) iv once every 3 weeks. These doses were equivalent to 36.05 mg/m2 of doxorubicin and 2.58 or 5.15 mg/m2 of mitoxantrone. Sequential endomyocardial biopsies were performed approximately 2 weeks after the fourth (or fifth), seventh, and ninth doses in order to monitor histopathologic and ultrastructural changes during the study. Myocardial lesions that progressed with time and dose were observed in heart samples from dogs that received doxorubicin, but not in dogs that received mitoxantrone. The myocardial lesions induced by doxorubicin were observed with cumulative doses as low as 144 mg/m2. Myocardial changes, which did not progress with time and cumulative dose, were observed in dogs that received either dose of mitoxantrone. The earliest observable evidence of doxorubicin-associated cardiotoxicity was seen morphologically in biopsy material before clinical signs of cardiotoxicity. No evidence of cardiotoxicity, either morphologic or clinical, was seen in dogs treated with the maximum tolerated dose of mitoxantrone during the course of treatment. The dog appears to be a suitable model for studying the chronic cardiotoxic effects of anthracyclines and for monitoring effects of compounds such as mitoxantrone, which show a spectrum of activity and mechanism of action similar to that of anthracycline compounds.

Animals↗

Pyogenic sacroiliitis.

Seven definite and three probable cases of pyogenic sacroiliitis are presented and compared to 72 cases found in the English literature. Patients may present with a subacute localized or an acute systemic illness. Six of our patients were parenteral drug abusers. Symptoms often were vague, but sacroiliac tenderness was invariably found on examination. Sacroiliac uptake of gallium67 citrate and/or technetium99m pyrophosphate suggested the diagnosis which was confirmed by fluoroscopically controlled joint aspiration when blood cultures were sterile. Gram-negative organisms, group B streptococci and a Staphylococcus were isolated. Antibiotic treatment for four to six weeks was uniformly successful. Surgery should be reserved for abscess or sequestrum formation, neither of which were encountered in this series.

Adult↗