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Biomedical subjects

I D Duncan

Publications and source records attributed to I D Duncan.

At least 91 records · Page 5Linked to original sources

Functional capacities of transplanted cell-sorted adult oligodendrocytes.

Previous work has shown that transplanted dissociated glial cells derived from neonatal rats can myelinate areas of the myelin deficient (md) rat spinal cord. In the present studies we have examined the ability of adult glial cells, either as suspension of mixed glial cells or as 01 positive oligodendrocytes purified by cell sorting, to myelinate md rat axons following transplantation. Mixed glial cell preparations from adult rats myelinated large areas of either, dorsal, lateral or ventral columns. These areas contained clumped, transplanted oligodendrocytes. In addition, preparations containing over 90% 01 positive oligodendrocytes were also capable of myelinating large numbers of axons upon transplantation. These results suggest that adult oligodendrocytes may play an important role in remyelination of the adult CNS.

Animals↗

Histologic evaluation of nerve muscle pedicle graft used as a treatment for left laryngeal hemiplegia in standardbreds.

A nerve muscle pedicle (NMP) graft was placed in the cricoarytenoideus dorsalis (CAD) muscle of 6 horses with induced left laryngeal hemiplegia. The NMP graft was created by use of the first cervical nerve and omohyoideus muscle. In 1 horse (control), the first cervical nerve was transected after placement of the NMP graft. One year after the surgical procedure, horses were examined endoscopically and then anesthetized. While the larynx was observed endoscopically, the first cervical nerve was stimulated. Horses were subsequently euthanatized, and the larynx was harvested. Prior to anesthesia, the endoscopic appearance of the larynx of all horses was typical of laryngeal hemiplegia. During anesthesia, stimulation of the first cervical nerve produced vigorous abduction of the left arytenoid in principal horses but not in the control horse. The right cricoarytenoideus lateralis and CAD muscles were grossly and histologically normal. Also, the left cricoarytenoideus lateralis was atrophic in all horses as was the left CAD muscle of the control horse. In contrast, the left CAD muscle harvested from principal horses had evidence of reinnervation with type 1 or type 2 fiber grouping. One year after the NMP graft procedure, horses with left laryngeal hemiplegia had reinnervation of the left CAD muscle. In another study, reinnervation was sufficient to allow normal laryngeal function during exercise. Combined, these data suggest that the NMP graft procedure is a viable technique for the treatment of left laryngeal hemiplegia in horses.

Animals↗

Effective destruction of cervical intraepithelial neoplasia (CIN) 3 at 100 degrees C using the Semm cold coagulator: 14 years experience.

A total of 1628 women with CIN 3 treated with the Semm cold coagulator between 1975 and 1989 was followed primarily by cytology. The standard suitability criteria for ablation were adhered to except that patients were treated at their first visit when the colposcopist expected that the diagnosis would be no worse than CIN 3. Overall 97% of the women were treated at their first visit. In 30 women (2%) the histology was glandular or worse than expected, but 22 of these showed no persistent cervical disease subsequently. Follow-up was achieved for 87% at 10 years. In actuarial terms the primary success rate was 95% at 1 year and 92% at 5 years, it was similar for all age groups. Repeat cold-coagulation for persistent/recurrent CIN 3 was less successful and is not advised. The outcome for 226 pregnancies established after treatment is known. The rates for miscarriage, preterm or operative delivery were not increased. Cold-coagulation of CIN 3 at 100 degrees C as performed by us is as effective as any other treatment and calls into question the need for more expensive practices.

Adult↗

Preferential denervation of the adductor muscles of the equine larynx. I: Muscle pathology.

The laryngeal muscles of 18 horses were examined histologically. The neurogenic changes found in each muscle were scored by four reviewers and the results evaluated statistically. Fifteen of these horses had endoscopic evidence of abnormal laryngeal function, three of which were defined as having adductor paralysis. Measurement of muscle fibre area in two horses with idiopathic laryngeal hemiplegia (ILH) was performed. In the quantitative study of neurogenic change, the adductor muscles were more significantly affected than the abductor muscle. This was also true in the clinical cases of ILH where measurement of muscle fibre area demonstrated that the lateral cricoarytenoid (adductor) muscles showed a wider range of pathological changes than the dorsal cricoarytenoid muscle (abductor). Those horses with the most severe muscle pathology also had the most abnormal endoscopic findings. The propensity for denervation of the adductor muscles should provide clues as to the pathogenesis and natural history of horses with sub-clinical laryngeal disease and ILH.

Analysis of Variance↗

Preferential denervation of the adductor muscles of the equine larynx. II: Nerve pathology.

The terminal branches of the recurrent laryngeal nerve (RLN) of three normal ponies and six horses with sub-clinical laryngeal disease were examined qualitatively and quantitatively in an attempt to explain the preferential denervation of the laryngeal adductor muscles in the neuropathy of idiopathic laryngeal hemiplegia (ILH). The myelinated fibre spectra of all the motor nerve fibres in the left and right abductor and adductor branches of the RLN in three normal ponies were measured. The density of myelinated fibres was also calculated. There was no significant difference between the larger group of myelinated fibres in the adductor or abductor branches. In the six horses with laryngeal hemiparesis, however, there was a marked preferential loss of the medium/large size myelinated fibres in the left adductor branch, although nerve fibre densities were not significantly different. While no simple morphometrical feature was found to explain the selective muscle denervation, the greater loss of large diameter myelinated fibres in the adductor branches confirms the earlier observation of adductor muscle susceptibility in the neuropathy of ILH.

Animals↗

A comparison of techniques to enhance the evaluation of equine laryngeal function.

This study was designed to define a simple, unequivocal test for the evaluation of laryngeal function and the diagnosis of idiopathic laryngeal hemiplegia (ILH). ILH is a disorder that results from left recurrent laryngeal neuropathy and in which there is no movement of the left arytenoid cartilage and vocal fold. Laryngeal function was evaluated in seven horses using four techniques designed to stimulate laryngeal movements:-nasal occlusion, exercise, swallowing and administration of a respiratory stimulant. In addition, the effects of sedation and twitching on the endoscopic examination were also examined. The cross-sectional area of the rima glottidis was measured in each horse at rest and after each technique was performed. There was no statistically significant difference in the increase in area seen after nasal occlusion or exercise. Doxapram hydrochloride increased the cross-sectional area of the rima glottidis, whereas xylazine caused a decrease. Neither of these pharmacological agents exaggerated or decreased the amount of asynchronous movement or tremoring of the arytenoid cartilages. Manual occlusion of the external nares during endoscopy is a simple, yet effective method of stimulating arytenoid function and hence diagnosing ILH.

Animals↗

Macromolecular structure of axon membrane and action potential conduction in myelin deficient and myelin deficient heterozygote rat optic nerves.

The macromolecular structure of the axon membrane in optic nerves from 25-day-old male littermate control and myelin deficient (md) rats and 16-month-old md heterozygotic rats was examined with quantitative freeze-fracture electron microscopy. The axon membrane of control optic nerves displayed an asymmetrical partitioning of intramembranous particles (IMPs); P-fracture faces of myelinated internodal axon membrane were more particulate than those of pre-myelinated axons (approximately 1600 v 1100 microns-2, respectively), while relatively few IMPs (approximately 150 microns-2) were present on external faces (E-faces) of internodal or pre-myelinated axon membrane. Amyelinated axons of md optic nerves also exhibited an asymmetrical partitioning of IMPs; protoplasmic membrane face (P-face) IMP densities, taken as a group, exhibited a wide range (approximately 600-2300 microns-2) and, in most regions, E-faces displayed a relatively low IMP density (approximately 175 microns-2). Axons of greater than 0.4 microns diameter exhibited significantly greater mean P-face IMP density than axons less than 0.4 microns diameter. Aggregations of E-face IMPs (approximately 350 microns-2) were occasionally observed along amyelinated axon membrane from md optic nerves. Optic nerves from md heterozygote rats exhibit myelin mosaicism, permitting examination of myelinated and amyelinated axon membrane along the same tract. The axon membrane exhibits different ultrastructure in these two domains. Myelinated internodal axon membrane from md heterozygote optic nerves exhibits similar P- and E-face IMP densities to those of control internodal axolemma (approximately 1800 and 140 microns-2, respectively). Amyelinated axons in the heterozygote exhibit a membrane structure similar to amyelinated axons in md optic nerve. P-face IMP density of large diameter (greater than 0.4 microns) amyelinated axons from md heterozygote optic nerves is significantly greater than that of small calibre (less than 0.4 microns) axons. In most regions, amyelinated axon membrane exhibits a relatively low E-face IMP density (approximately 200 microns-2); however, focal aggregations (approximately 400 microns-2) of E-face particles are present. Electrophysiological recordings demonstrate that amyelinated axons in md optic nerves support the conduction of action potentials. Compound action potentials in md optic nerves exhibit a monophasic configuration, even at 20-days postnatal, similar to that of pre-myelinated optic nerve of 7-day-old normal rats. Moreover, conduction velocities in the amyelinated 20-day-old md optic nerve are similar to those displayed by pre-myelinated axons from 7-day-old optic nerves.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Malignant jugulotympanic paraganglioma in a dog.

An invasive malignant epithelial neoplasm was diagnosed as a paraganglioma by light and electron microscopy and immunohistochemically by a positive reaction with anti-neuron-specific enolase. Due to the extensive involvement of the middle ear, a primary origin in the jugulotympanic or jugular paraganglia is suggested.

Animals↗

How frequently need vaginal smears be taken after hysterectomy for cervical intraepithelial neoplasia?

A retrospective longitudinal review identified 341 women who had had a hysterectomy in association with CIN 3, in Tayside Region, during the years 1967-1977; 219 (64%) had completed 10 years of cytology follow-up and of 140 women eligible for 15-year smears 79 (56%) completed the 15-year follow-up. Eight (4%) of the 219 patients developed abnormal cytology, but in six, smears reverted to normal spontaneously. Two patients had persistently abnormal smears and vaginal intraepithelial neoplasia (VAIN) was diagnosed. Only one patient completing 15-year follow-up had an abnormal smear and VAIN later diagnosed. No patient over this 15-year period developed invasive vaginal carcinoma. Sixty vaginal carcinomas were identified during the period 1957-1987 from the gynaecology cancer register; only one was associated with a previous diagnosis of CIN 3 at hysterectomy. With such data we would propose screening 6-monthly during the first post-operative year and then at 2 years. If these smears were normal, the patient could then revert to the normal screening programme.

Adult↗

A point mutation in the proteolipid protein gene of the 'shaking pup' interrupts oligodendrocyte development.

The differentiation of the oligodendrocyte from its bipotential progenitor culminates in the production of the myelin-specific proteins and the elaboration of membrane processes that ensheath the axon. Mutations in proteolipid protein (PLP) and its alternatively spliced isoform DM-20, the major protein constituents of central nervous system myelin, are characterized by a significant reduction in the number of mature oligodendrocytes, resulting in severe hypomyelination, tremor and early death. The canine shaking pup carries such a mutation, a single base change that substitutes a proline for a histidine near the first transmembrane region of PLP and DM-20. This mutation hinders oligodendrocyte differentiation, as evidence by a splicing pattern at the PLP locus characteristic of immature oligodendrocytes. The spliced transcript expressed earliest in development, DM-20, continues to be overexpressed in shaking pup oligodendrocytes. The disruption of the normal maturation schedule in these X-linked dysmyelinating disorders suggests that PLP or DM-20 plays a fundamental role in oligodendrocyte development. We propose that, while the more abundant PLP is the primary structural component of myelin, DM-20 may be critical to oligodendrocyte maturation.

Amino Acid Sequence↗

Identification of octadeca-9,11-dienoic acid and its significance in the diagnosis of cervical intraepithelial neoplasia.

In 1987 it was claimed using high performance liquid chromatography (HPLC) that the molar ratio of octadeca-9,11-dienoic acid to its parent linoleic acid (18:2 (9,12)) was raised in malignant and premalignant conditions of the cervix. In this study based on a gas chromatographic procedure which prevents autoxidation and avoids the detection limitations of HPLC, we have shown that assay of these fatty acids has no role to play in the assessment of cervical neoplasia.

Carcinoma, Squamous Cell↗

Myelination in the jimpy mouse in the absence of proteolipid protein.

A point mutation in the gene for proteolipid protein (PLP) has been suggested to account for the dysmyelination seen in the jimpy mouse mutant. Despite the absence of PLP, the major integral membrane protein of central nervous system (CNS) myelin, this study shows that there are many scattered myelinated fibers present in the spinal cord of this murine mutant which are immunocytochemically positive for myelin basic protein (MBP), yet negative for PLP. This lack of PLP results in an abnormal compaction of the extracellular leaflets of the myelin sheath and the formation of an abnormal intraperiod line. These results are similar to those seen in another X-linked myelin mutant, the myelin-deficient rat (Duncan et al.: Proc. Natl. Acad. Sci. U.S.A., 84:6287-6291, 1987), and show that a multilamellar membrane can be formed in the absence of its major integral membrane protein.

Animals↗

Hypomyelination in the neonatal rat central and peripheral nervous systems following tellurium intoxication.

Neonatal rats were exposed to Tellurium (Te), via the mother's milk, from the day of birth until sacrifice at 7, 14, 21, and 28 days of age. Light and electron microscopy revealed Schwann cell and myelin degeneration in the sciatic nerves at each age studied. These changes were similar to those described in weanling rats as a result of Te intoxication. In the CNS, hypomyelination of the optic nerves was convincingly demonstrated at 14, 21, and 28 days of age, accompanied by some evidence of myelin degeneration. These changes were also seen in the ventral columns of the cervical spinal cords, although less markedly, and were confirmed by quantitative methods. There was little evidence of oligodendrocyte pathology in the CNS, and it appears that degeneration of these cells is not the primary cause of the CNS hypomyelination, in contrast to the PNS where Schwann cell degeneration has been shown to precede the myelin pathology.

Animals↗

Polyneuropathy in feline Niemann-Pick disease.

Two related cats, aged 5 months and 7 months, and 1 unrelated cat, aged 4 months, presented with signs of a progressive neuromuscular disease. Detailed electrophysiological studies suggested a primary demyelinating polyneuropathy, which was confirmed by muscle and nerve biopsies and on necropsy examination. Light and electron microscopic findings indicated a lysosomal storage disease, which was diagnosed as sphingomyelinase deficiency (Niemann-Pick disease) by enzyme analysis and lipid fractionation, although significant biochemical differences existed between the 2 related cats and the third cat. Several lines of evidence suggest that these 2 related cats were affected with a variant of type A Niemann-Pick disease, whereas cat 3 represented classic Niemann-Pick disease type A.

Animals↗

The increasing problem in Tayside of cervical cancer in younger women.

The incidence of cervical carcinoma in younger women is increasing in Tayside despite a decrease in the overall incidence. However, stage for stage, we did not encounter a poorer survival in younger patients. A number of patients had been sterilised or had a pregnancy when cytological screening was available and not made use of. There were also some false negative smears which were reclassified for retrospective analysis. We would recommend cervical screening every three years and careful inspection of the cervix and a smear taken in cases of abnormal gynaecological symptoms such as post coital bleeding.

Adenocarcinoma↗

Schwann cell myelination of the myelin deficient rat spinal cord following X-irradiation.

The myelin-deficient (md) rat is an X-linked myelin mutant that has an abnormality of oligodendrocytes and a severe paucity of myelin throughout the CNS. This lack of myelin makes it an ideal model in which to study the cellular interactions that occur when "foreign" myelinating cells are induced in the milieu of this nonmyelinated CNS. In this study, Schwann cells were induced in the lumbosacral spinal cord by exposing it to radiation, a technique demonstrated repeatedly in other nonmutant strains of rats. Md rats and their age-matched littermates were irradiated (3,000 to 4,000 R) at 3 days of age and perfused 16-22 days later after pulse labeling with tritiated thymidine. In the md rat, Schwann cell invasion progressed from the area of the spinal cord-nerve root junction and extended into the dorsal columns and adjacent gray matter. Autoradiographic evidence revealed that many of these cells incorporated 3H-thymidine, indicating that they were undergoing proliferation. Ultrastructural observations showed that there was an integration of these intraspinal Schwann cells with the cells normally occurring in this environment, i.e., oligodendrocytes and astrocytes. The extent of migration and division of Schwann cells, as well as their interactions with glial cells, were similar to those seen in the nonmutant irradiated littermates. These studies provide conclusive evidence that md rat axons are normal with respect to their ability to provide trophic and mitogenic signals to myelinating cells.

Animals↗