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Biomedical subjects

K D Barron

Publications and source records attributed to K D Barron.

At least 37 records · Page 2Linked to original sources
PubMed1987

Mitochondrial encephalomyopathy and partial cytochrome c oxidase deficiency.

A 52-year-old man had slowly progressive weakness and wasting of limb-muscles, sensorineural hearing loss, and complex partial seizures. CT showed cerebral atrophy, but he was not demented. Muscle biopsy showed ragged-red fibers and decreased histochemical stain for cytochrome c oxidase. Biochemical studies showed decreased cytochrome c oxidase activity in crude muscle extracts and in isolated mitochondria (44 and 30% of normal), while other mitochondrial enzymes were normal. A comparable decrease of immunologically reactive enzyme protein was shown by immunotitration with antibodies against human heart cytochrome c oxidase. Partial defects of cytochrome c oxidase may cause adult-onset, slowly progressive mitochondrial encephalomyopathies.

Atrophy↗
PubMed1986

Qualitative and quantitative ultrastructural observations on retinal ganglion cell layer of rat after intraorbital optic nerve crush.

Rat retinal ganglion cell layer (GCL) was examined ultrastructurally 1-180 days after intraorbital crushing of one optic nerve. It was confirmed quantitatively that axotomized ganglion cells lost cisternal membranes of the rough endoplasmic reticulum (RER) and showed disintegration of Nissl bodies and ribosomal rosettes 3 days postoperatively. Between 60 and 180 days after neurotomy there was partial reversion of the RER towards normal. At postoperative intervals of 14-60 days, chromatin aggregation became conspicuous and some nuclei were prominently furrowed and contained electron-dense inclusions. Concurrently, profiles of dead ganglion cells were encountered. Mean mitochondrial area increased in axotomized neurons but mitochondrial density declined, while the Golgi apparatus, lamellar specializations of the RER and the size of nuclei did not change significantly. Cytoplasmic atrophy was profound, however. Small nerve cells of the GCL appeared morphologically distinct from ganglion cells and did not undergo appreciable alteration. A decline in neuronal density, approximating 35%, occurred between the third and seventh postoperative day and progressed slowly thereafter. Neuronal density was 32% of normal 180 days postoperatively. A temporary increase in glial density 3-28 days after operation was due to microglial hyperplasia. Müller cell and astrocytic processes hypertrophied, infiltrated nerve fibre bundles, and surrounded and intruded into neuronal somata. Bundles of unmyelinated small axons, invested by astrocytes and basal lamina, were present within the necrotic cavity of the lesioned nerve 28-90 days postoperatively and had cytologic features of regenerative axonal sprouts. We conclude that intraorbital optic nerve crush is followed by a noteworthy degree of regenerative axonal sprouting which occurs and persists against a background of slow but relentless decline in the retinal ganglion cell population. This slow decline follows a rapidly-sustained loss of approximately one-third of the axotomized retinal ganglion cells during the first postoperative week. Intraorbital, as opposed to intracranial, injury of the optic nerve appears, paradoxically, to induce both a greater degree of ganglion cell death and a greater amount of regenerative axonal sprouting. Cytologic changes in axotomized retinal ganglion cells resemble those described for other populations of mammalian intrinsic neurons subjected to like injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Muscle pathology in Bassen-Kornzweig syndrome and vitamin E deficiency.

A constellation of histologic abnormalities was demonstrated in the quadriceps femoris muscle of a 29-year-old man with Bassen-Kornzweig syndrome. The abnormalities consisted of fibers containing dense lipid inclusions ceroid and lipofuscin, a spectrum of fiber size, architectural changes, and an increase in central nuclei. A dramatic shift of fiber type predominance, from type I to type II, was demonstrated in the myosin ATPase reactions one year after vitamin E therapy. Despite an apparent reduction in the number of fibers containing lipid and ceroid granules in the second biopsy, neuromyopathic changes worsened. The relationship of these findings to vitamin E therapy is discussed.

Abetalipoproteinemia↗
PubMed1986

Olivopontocerebellar atrophy: immunocytochemical and Golgi observations.

Brain tissue was obtained promptly after death from a patient with autosomal dominant olivopontocerebellar atrophy and studied by immunocytochemistry and a Golgi technique. Antiglutamic acid decarboxylase showed severe loss of Purkinje cells and their terminals in the dentate nucleus. Stains for neuron-specific enolase (NSE) and microtubule-associated proteins (MAP) confirmed the integrity of the dentate nucleus. Basket and stellate cells revealed secondary changes, but Golgi neurons were intact. Methods for NSE and MAP disclosed dendritic alterations and loss of neurons in the basis pontis and inferior olivary nuclei. Golgi impregnation of Purkinje cells showed loss of major dendrites, paucity of spiny branchlets, and axonal expansions.

Aged↗
PubMed1985

Glial and axonal development in optic nerve of myelin deficient rat mutant.

Development of glial cell lines and axons is reported for the optic nerve of the myelin deficient rat mutant, md, 3-46 days postnatally. In mutants, optic nerves do not increase in area after 16 days of age whereas, in normal rats, they enlarge through 46 days of postnatal life. The density of glial cells, determined in cross-sections, is similar in md and normal littermates through 19 days postnatally. Thereafter, glial densities are greater in the mutant. Nonetheless, total glial counts are reduced in md as compared to the normal, because cross-sectional areas and lengths of mutant nerve 30-46 days after birth are smaller than those of age-matched, normal littermates. Differential counts of glial cells, made by ultrastructural criteria, show that md optic nerves contain abnormal, vacuolated, immature oligodendroglia from the third postnatal day. Furthermore, oligodendrocytes are reduced in number in older mutants; they constitute 1% of optic nerve neuroglia at 46 days. Astrocytic numbers are increased in relative, not in absolute, terms from 19 days, and microglial numbers are greater than normal in the oldest mutants. Reactive microglia, containing large cytoplasmic lipid droplets, constitute 4-8% of the glia of md nerve 19-46 days postnatally. Mean axonal areas are similar in normal rats and mutants at 19 and 43-46 days of age. However, mitochondrial density is greater in md axons 19 days after birth and mean areas of axonal mitochondria are significantly larger in 43-46 day mutants than in age-matched, normal littermates. Additionally, the percent area of axoplasm occupied by mitochondria is increased in md at both 19 and 43-46 days of age. The myelination defect in md appears to be due primarily to an oligodendroglial abnormality which precedes the normal age of onset of myelination. Astrocytic and microglial changes are secondary. Axonal enlargement proceeds normally over 46 days of postnatal life. Overall, the data do not provide definitive support for an axonal basis for the myelination defect, although measurable differences in axonal mitochondria between mutants and normals are demonstrable and qualitative abnormalities do occur in the axons of the mutant.

Age Factors↗
PubMed1985

RNA content of normal and axotomized retinal ganglion cells of rat and goldfish.

The responses of rat and goldfish retinal ganglion cells to axotomy were examined by a quantitative cytochemical method for RNA and by morphometric measurement 1-60 (rat) and 3-90 (goldfish) days after interruption of one optic nerve or tract intracranially. Unoperated control animals were studied also. The RNA content of axotomized neurons of rat fell 7-60 days postoperatively. Additionally, atrophy of the axotomized somas occurred. Over time, neuronal atrophy approximately paralleled the loss of RNA, and mean cell area and RNA content were reduced by about 25% 60 days after axotomy. Incorporation of 3H-uridine by axotomized neurons declined also. Axotomized retinal ganglion cells of goldfish behaved differently from those of the rat and showed increases in RNA content, most conspicuously 14-60 days postoperatively. Enlargement of axotomized fish neurons occurred but was less proportionately than concomitant increases in RNA content. The nonaxotomized ganglion cells of goldfish displayed statistically significant increases in size and RNA content 14-49 days after unilateral optic nerve or tract lesions. In contrast, alterations in rat retinal ganglion cells contralateral to interruption of one optic nerve were of limited and questionable significance. The contrasting reactions to axotomy by the retinal ganglion cells of these two vertebrates, one of which regenerates optic axons and one of which does not, may support the proposition that the somal response to axon injury has an important bearing upon the success or failure of CNS regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Glucose utilization is unchanged in red nucleus after axotomy.

Separate series of adult rats were subjected to unilateral high cervical and low thoracic section of the rubrospinal tract and sacrificed 1-30 (cervical series) and 3-100 days (thoracic series) later. Local cerebral glucose utilization ([14C]2-DG method of Sokoloff et al.) was determined in the red nucleus and in the inferior colliculus, nucleus interpositus and sensorimotor cortex of both sides in operates and controls. Although severe atrophy of rubral neurons follows cervical tractotomy while reversible chromatolytic alterations occur after thoracic lesions, glucose utilization did not differ in the red nucleus of operated and control rats. However, glucose utilization increased slightly in the inferior colliculus of all operated animals, a finding of indeterminate significance. The failure of axotomized intrinsic neurons of red nucleus and their surround to show altered glucose utilization stands in sharp contrast to the marked increase which occurs in cranial nerve nuclei after axotomy of their contained extrinsic neurons. The data are held to constitute another indication that there is a fundamental difference in the metabolic responses of extrinsic and intrinsic mammalian neurons to axotomy and may support the contention that, in mammals, the axon reaction of intrinsic neurons is fundamentally different from that of extrinsic nerve cells. This difference may have significance for failure of axon regeneration in mammalian CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Axon reaction in hypoglossal and dorsal motor vagal neurons of adult rat: incorporation of [3H]leucine.

Pairs of adult rats received [3H]leucine (i.p., 5 microCi/g body weight) 0.25, 1, and 16 h before killing and zero (unoperated control animals) and 1 to 164 days after unilateral cervical vagotomy and hypoglossal neurotomy. Grain counts and morphometric measurements were made on axotomized and uninjured neurons in histoautoradiographs of the medullary nuclei. Axotomized hypoglossal neurons, which largely survive the injury, both enlarged and incorporated increased amounts of tritiated leucine at each labeling interval, 3 through 28 days postoperatively. In the vagal dorsal motor nucleus (DMN), axotomized cells, which frequently die after neurotomy, enlarged slightly through 28 days postoperatively, then atrophied; DMN neurons increased amino acid uptake for a shorter period (days 7 through 14) than hypoglossal neurons. This increase achieved statistical significance only when the labeling intervals were 0.25 or 1.0 h. Neurons of the DMN contralateral to vagotomy also enlarged. Axotomized DMN neurons did not sustain increased protein synthesis as long as their hypoglossal counterparts and seemed to fail to increase synthesis of structural proteins with long half-lives (16-h labeling interval). The frequently necrobiotic response of axotomized DMN neurons may relate to these phenomena. From these and earlier results, we conclude that axon reaction appears to differ fundamentally in peripheral and central neurons. This difference may have significance for research on regeneration in the central nervous system.

Animals↗
PubMed1984

2',3'-cyclic nucleotide 3'-phosphodiesterase and 5'-nucleotidase in the central nervous system of a myelin-deficient rat mutant.

2',3'-Cyclic nucleotide 3'-phosphodiesterase activity was examined in brains and spinal cords of normal and myelin-deficient Wistar rats. While the activity in normal brains increased from 0.2 mumol/min/mg protein (units) at 6-10 days to 3.5 units at 25 days of postnatal age, the activity in the myelin-deficient rat remained at 0.2-0.3 units over the same period. In spinal cord, the normal activities were 5.7 and 10.9 units at 12 and 20 days, respectively, whereas they declined in the myelin-deficient rat from 1.06 to 0.79 units for the same age points. 5'-Nucleotidase activities in brain and spinal cord were normal in the myelin deficient rat at both ages.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1983

Nonpharmacologic treatment of chronic headache: prediction of outcome.

We studied the ability of headache history, a 4-week headache diary, standard psychological tests, and laboratory measures of psychophysiologic responses to stress to predict the outcome of relaxation therapy and biofeedback for three types of chronic headache. Using canonical discriminant function analyses, each potential predictor set was tested separately, and all four were tested together. Information from the headache history alone correctly classified 89 to 95% of patients as improved or unimproved. No other single predictor set was consistently better than headache history. When all four predictor sets were combined, prediction improved; 93 to 100% of patients were correctly classified.

Adult↗
PubMed1982

Morphometric measurements and RNA content of axotomized feline cervical motoneurons.

Microspectrophotometric estimates of RNA content and morphometric measurements of cytoplasmic, nuclear and nucleolar areas were made on 30 to 60 motoneurons (somal areas greater than 1000 microns2) ipsilateral and contralateral to brachial plexotomy performed unilaterally on adult cats 2-90 days before sacrifice. Nerve cells of unoperated animals were also assayed. Somal and cytoplasmic areas of axotomized motoneurons were larger than those of the corresponding, contralateral motor nerve cells 4, 6 and 75 days postoperatively. Because of between animal variability, it could not be determined, however, whether this difference was due to an increase in the area of the axotomized motoneurons or to a decrease in the area of the contralateral nerve cells. Nucleolar sizes did not change. In contrast, nuclei of axotomized motoneurons showed a temporary but unequivocal areal decrease. The cytoplasmic RNA content of axotomized motoneurons fell 14-28 days postoperatively but rose thereafter, being increased slightly but significantly 75-90 days after operation. At no postoperative interval, however, did the nucleolar RNA content of the axotomized cells deviate unequivocally from the unoperated or zero day condition. The following points may be emphasized: 1. these results differ from similar measurements of axotomized motoneurons of rodents and lagomorphs; 2. the data do not provide certain evidence of change in either morphometric parameters or RNA content of motoneurons on the side contralateral to surgery, although the possibility of a decrease in the size of these uninjured neurons should be considered; 3. morphometric and RNA measurements on axotomized peripheral (extrinsic) neurons of spinal anterior horn of cat contrast with similar measurements on axotomized central (intrinsic) neurons of cat red nucleus.

Animals↗
PubMed1982

Ultrastructure of the central nervous system in a myelin deficient rat.

Myelin deficiency (md) is a new mutant in the Wistar rat caused by an X-linked recessive lethal gene. One-half of the male offspring develop tremor and ataxia at 10-12 days of age and seizures at 16-21 days. Usually, the animals die 24-28 days postnatally unless survival is prolonged by anticonvulsants. Light microscopic examination of the C.N.S. shows a complete lack of myelin. The P.N.S. is normally myelinated, however. Frontal cortex, corpus callosum, optic nerves, cerebellum and spinal cord were studied routinely in affected animals aged 3-46 days. Abnormal males were identified three days after birth by the absence of myelinated axons from the ventral funiculus of the cervical cord. In mutants aged 3-16 days, axons had the usual ultrastructural features but were either entirely non-myelinated or, rarely, were invested by poorly organized, non-compacted, myelin-like loops of membranes, 2 to 4 in number. In mutants aged 17-20 days, axonal swellings appeared. These increased in number with longer survival times and contained large numbers of microtubules, neurofilaments, mitochondria and dense bodies. Normal C.N.S. myelin was not observed at any age. Two types of abnormal glial cell occur in md. The first, present in white matter at three days of age, is an abnormal oligodendrocyte. The cytoplasm contains dilatation of the rough-surfaced endoplasmic reticulum and the nuclear envelope is widened. A second cell-type, conspicuous by 10 days, has an electron-dense nucleus with prominently clumped chromatin and large cytoplasmic lipid droplets. This second cell type is believed to be a microgliacyte. The number of cytologically-normal oligodendrocytes decreases as mutants age while hypertrophied, filament-rich astrocytes occur in increasing numbers. The myelin defect in md C.N.S. is probably due to an abnormality of oligodendrocytes. Axonal alterations are probably secondary. Myelin deficiency resembles the murine mutant, Jimpy (jp), although ultrastructural changes in oligodendrocytes appear to be dis-similar and md, in contrast to jp, contains no normal-appearing C.N.S. myelin.

Aging↗
PubMed1982

Fine structure of neurons of the hypertrophied human inferior olive.

Ultrastructural study of hypertrophied inferior olives from three cases of palatal myoclonus revealed tha nerve cells not infrequently contained numerous round, homogeneously electron-dense granules (mean diameter, 360 nm) located within expanded cisternal profiles of rough endoplasmic reticulum (RER). Control tissue did not contain similar structures. These granules may consist of proteinaceous secretion of the RER which, for reason unknown, accumulates during transsynaptic degeneration of the inferior olive. Additional noteworthy electron microscopic features of neurons of the hypertrophied olive were as follows: 1. neurofilamentous hyperplasia, greater in dendrites than in perikarya; 2. vacuoles in intermediate and large (up to 15 mum) size, derived from RER; and 3. prominent intracytoplasmic protrusions by boutons containing dense core vesicles (mean diameter, 98 nm). Glomeruloids were identified ultrastructurally and consisted of numerous boutons interspersed among neurofilament-rich dendrites and occasional, filament-packed astrocytic profiles. Frequently, these boutons also contained dense-core vesicles. It seems possible that the boutons mentioned may arise from collateral axonal sprouts.

Adult↗