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Biomedical subjects

M I Johnson

Publications and source records attributed to M I Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Cystic brain stem necrosis in a premature infant after prolonged bradycardia.

A case is described of symmetrical cavitating brain stem necrosis produced by cardiac arrest in a premature infant. Two months after birth this 25-week gestational age infant suffered a prolonged episode of bradycardia. She was resuscitated and then died 3 weeks later. The autopsy revealed striking bilateral cavitation of the brain stem tegmentum extending in a columnar fashion from the upper portion of the spinal cord to the hypothalamus. The findings in this case are identical to the brain stem injury experimentally produced by complete cardiac arrest in the rhesus monkey.

Bradycardia↗
PubMed1992

Long term use of transcutaneous electrical nerve stimulation at Newcastle Pain Relief Clinic.

This retrospective study of long-term use of transcutaneous electrical nerve stimulation (TENS) at Newcastle Pain Relief Clinic indicates that TENS has been a successful analgesic treatment for 58.6% of 1582 patients attending the clinic over a period of 10 years. A wide range of pain conditions were found to respond to TENS and many patients continued to use the treatment for several years. Most patients not responding to TENS (during a home trial) returned stimulators at the first follow-up appointment. Thus TENS should be considered as a simple, safe and reusable first line treatment for many pain conditions.

Ambulatory Care Facilities↗
PubMed1991

Analgesic effects of different pulse patterns of transcutaneous electrical nerve stimulation on cold-induced pain in normal subjects.

The analgesic efficacy of various pulse patterns of transcutaneous electrical nerve stimulation (TENS) were assessed in 84 normal healthy subjects using the cold pressor pain technique. Burst, modulation, random and continuous TENS all significantly elevated ice pain threshold. Continuous (80 Hz) TENS produced the greatest mean elevation in threshold but the response to random TENS showed the least inter-subject variation. Ice pain tolerance was increased by all modes of TENS, continuous TENS producing the greatest magnitude of response, although these changes did not reach statistical significance. Increasing the size of electrodes reduced the effect of continuous TENS. The clinical implications of these findings are discussed.

Adolescent↗
PubMed1991

An in-depth study of long-term users of transcutaneous electrical nerve stimulation (TENS). Implications for clinical use of TENS.

This in-depth study examines the relationships between patient, stimulator and outcome variables in a large number of chronic pain patients utilising TENS on a long-term basis. 179 patients completed a TENS questionnaire designed to record age, sex, cause and site of pain and TENS treatment regime. Of these 179 patients, 107 attended our research unit for assessment of the electrical characteristics of TENS during self-administered treatment. Although a remarkable lack of correlation between patient, stimulator and outcome variables was found to exist, the analysis revealed much information of importance: 47% of patients found TENS reduced their pain by more than half; TENS analgesia was rapid both in onset (less than 0.5 h in 75% patients) and in offset (less than 0.5 h in 51% patients); one-third of patients utilised TENS for over 61 h/week; pulse frequencies between 1 and 70 Hz were utilised by 75% of patients; 44% of patients benefitted from burst mode stimulation. The clinical implications of these findings are discussed.

Adult↗
PubMed1991

The consistency of pulse frequencies and pulse patterns of transcutaneous electrical nerve stimulation (TENS) used by chronic pain patients.

This study records the consistency of transcutaneous electrical nerve stimulation (TENS) pulse frequency and pulse pattern used by 13 chronic patients over a 1 year period. The results show that patients prefer specific pulse frequencies and pulse patterns unique to the individual and that they turn to such frequencies and patterns on subsequent treatment sessions. Pulse frequencies and pulse patterns were not related to the cause and site of pain, a finding consistent with previous study in this laboratory. This observation, coupled with the large variability in pulse frequencies and pulse patterns used between individuals, implies that patients prefer such frequencies and patterns for reasons of comfort which may not be related to mechanisms specific to the pain system.

Adult↗
PubMed1991

The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects.

The present study examines the effects of auricular transcutaneous electrical nerve stimulation (TENS) on electrical pain threshold measured at the ipsilateral wrist and autonomic functions including skin temperature, blood pressure and pulse rate in 24 healthy subjects. TENS was administered as low frequency trains of pulses delivered at a 'strong but comfortable' intensity to 1 of 3 auricular points to be examined: (i) autonomic effects (autonomic point), (ii) pain threshold effects (wrist point), and (iii) placebo effects at an unrelated point (face point). A fourth untreated group was designated as a situation control. The main finding of the study was that auricular TENS produced no significant overall effects on experimental pain threshold or autonomic functions recorded under the present conditions. However, pain threshold was found to increase by over 50% of its pretreatment baseline in 4 subjects and by 30% in 6 subjects. This rise was not dependent upon the site of auricular TENS. The possible mechanisms of such changes are discussed.

Adolescent↗
PubMed1989

Astrocytes induce dendritic development in cultured sympathetic neurons.

Sympathetic neurons in culture require the influence of Schwann cells in order to develop dendrites comparable to those seen in vivo. This study demonstrates that astrocytes induce dendritic development in greater than 90% of sympathetic neurons after two weeks of co-culture. We conclude that dendrite inducing factors are distributed on both central and peripheral glia.

Animals↗
PubMed1989

Age-dependent changes in the capacity of rat sympathetic neurons to form dendrites in tissue culture.

We compared the ability of prenatal and postnatal rat sympathetic neurons to form dendrites in tissue culture. Dendrites were distinguished from axons by light microscopic criteria after intracellular dye injection and by differential immunostaining with antibodies to microtubule-associated protein-2 and to both non-phosphorylated and phosphorylated forms of the M and H neurofilament subunits. When maintained in the absence of serum and non-neuronal cells, most (72%) prenatal neurons were unipolar and had only an axon. In contrast, most (89%) neurons derived from postnatal ganglia were multipolar and extended both axons and dendrites. The dendritic morphology of postnatal neurons was usually simple with cells commonly having 2-5 short (50-200 microns), relatively unbranched dendrites. Thus, as the development of the dendritic arbor progresses in situ, sympathetic neurons acquire an enhanced ability to extend dendrites in tissue culture. To determine whether changes in the capacity to develop dendrites might occur with aging in vitro, ganglia were removed from prenatal rats and grown as explants for 3 weeks in the presence of non-neuronal cells; under these conditions, prenatal neurons within the explant became multipolar. When neurons derived from aged explants were subsequently maintained in dissociated cell culture, most formed dendrites. In cultures treated with an antimitotic agent, neurons typically had 1-4 unbranched dendrites; greater amounts of dendritic growth occurred in cultures in which ganglionic non-neuronal cells were allowed to proliferate. We conclude that: (1) the acquisition of the capacity to form dendrites in dissociated cell culture does not require either normal afferent input or physical contact with the target tissue; and (2) even after aging in vitro, sympathetic neurons remain responsive to the dendrite-promoting activity of ganglionic non-neuronal cells.

Adrenergic Fibers↗
PubMed1989

Rapid growth cone translocation on laminin is supported by lamellipodial not filopodial structures.

To determine the relationship between growth cone structure and motility, we compared the neurite extension rate, the form of individual growth cones, and the organization of f-actin in embryonic (E21) and postnatal (P30) sympathetic neurons in culture. Neurites extended faster on laminin than on collagen, but the P30 nerites were less than half as long as E21 neurites on both substrata. Growth cone shape was classified into one of five categories, ranging from fully lamellipodial to blunt endings. The leading margins of lamellipodia advanced smoothly across the substratum ahead of any filopodial activity and contained meshworks of actin filaments with no linear f-actin bundles, indicating that filopodia need not underlie lamellipodia. Rapid translocation (averaging 0.9-1.4 microns/min) was correlated with the presence of lamellipodia; translocation associated with filopodia averaged only 0.3-0.5 microns/min. This relationship extended to growth cones on a branched neurite where the translocation of each growth cone was dependent on its shape. Growth cones with both filopodial and lamellipodial components moved at intermediate rates. The prevalence of lamellipodial growth cones depended on age of the neurites; early in culture, 70% of E21 growth cones were primarily lamellipodial compared to 38% of P30 growth cones. A high percentage of E21 lamellipodial growth cones were associated with rapid neurite elongation (1.2 mm/day), whereas a week later, only 16% were lamellipodial, and neurites extended at 0.5 mm/day. Age-related differences in neurite extension thus reflected the proportion of lamellipodial growth cones present rather than disparities in basic structure or in the rates at which growth cones of a given type moved at different ages. Filopodia and lamellipodia are each sufficient to advance the neurite margin; however, rapid extension of superior cervical ganglion neurites was supported by lamellipodia independent of filopodial activity.

Actins↗
PubMed1989

Analgesic effects of different frequencies of transcutaneous electrical nerve stimulation on cold-induced pain in normal subjects.

The efficacy of transcutaneous electrical nerve stimulation (TENS) in producing analgesia in cold-induced pain was assessed using a range of 5 stimulating frequencies (10 Hz, 20 Hz, 40 Hz, 80 Hz and 160 Hz) in 83 normal healthy subjects. TENS significantly elevated ice pain threshold when compared with sham and control groups. TENS frequencies between 20 and 80 Hz produced greatest analgesia, while frequencies below and above this level (10 Hz and 160 Hz), although significantly elevating ice pain threshold, produced effects of a lesser magnitude. The frequency of pulse delivery was the governing factor as no significant differences in stimulus intensity were observed across the treatment groups. Measurement of ice pain tolerance was found to be unreliable under the present conditions. No significant relationships were observed between personality variables as measured by Eysenck Personality Questionnaires and the degree of TENS response.

Adolescent↗
PubMed1988

Glial cells promote dendritic development in rat sympathetic neurons in vitro.

Many types of glial-neuronal interactions occur during the development of the nervous system. To determine how such interactions might affect the development of autonomic ganglia, we compared the morphology of embryonic rat sympathetic neurons grown in the absence and in the presence of ganglionic nonneuronal cells in serum-free medium. Dye injections, electron microscopy, and immunocytochemistry were used to distinguish axons from dendrites. In cultures without nonneuronal cells, most (greater than 80%) sympathetic neurons extended only a single axonal process, and this unipolar state persisted for at least 8 weeks. Coculture with ganglionic nonneuronal cells caused sympathetic neurons to become multipolar and to extend multiple (range 1-17) dendrites. Morphometric measurements made after 1 month of coculture indicated that the amount of dendritic growth that occurred in vitro (mean number of dendrites/cell = 7.5; total dendritic length = 1,050 micron) was similar to that normally occurring during a comparable period in situ. In contrast to its prominent effects on dendritic growth, coculture did not cause changes in the number of axons/neuron or in the uptake of neurotransmitter. Cultures with ganglionic nonneuronal cells were immunostained for antigens present on the surfaces of fibroblasts (Thy-1.1, fibronectin) and of glia of the peripheral nervous system (laminin). Fewer than 1% of the nonneuronal cells displayed immunoreactivity for fibroblastic antigens; in contrast, greater than or equal to 99% reacted with antibody to laminin. Moreover, reconstitution experiments revealed that purified populations of laminin-positive Schwann cells promoted dendritic growth. Fibroblasts and heart cells lacked this activity. These data indicate that glia selectively promote dendritic development in sympathetic neurons maintained in serum-free medium.

Animals↗
PubMed1988

Distribution and phosphorylation of the growth-associated protein GAP-43 in regenerating sympathetic neurons in culture.

Sympathetic neurons regenerating in culture were studied in order to gain further insight into the intracellular distribution and phosphorylation of GAP-43, a protein that has been suggested to have a role in axonal outgrowth and neuronal plasticity (Willard et al., 1987). Superior cervical ganglion neurons from embryonic rats were highly reactive with a polyclonal antibody against the growth-associated protein GAP-43 soon after they were placed in culture on a laminin substrate. As these neurons extended neurites, the distribution of GAP-43 reactivity changed. The cell body became progressively less reactive, whereas the growth cone at the tip of the growing neurite reacted strongly. The pattern of immunofluorescence was punctate both in the growth cone and the adjacent neurite, but appeared more diffusely distributed in the cell body. The antibody reacted only with cells that had been subjected to treatment that permeabilized the plasma membrane. When antibody was supplied in the medium of growing neurons, it neither bound to the cells nor altered normal neurite initiation or elongation. Of the different types of cells in these cultures, the antibody reacted only with neurons; it did not react with Schwann cells or fibroblasts. The stimulation of protein kinase C in these cultures resulted in a 7-fold stimulation of the phosphorylation of a protein of similar electrophoretic mobility to GAP-43. These observations demonstrate that GAP-43 is neuron-specific, is present throughout the neuron but at higher levels in the growth cone, and is a major substrate of protein kinase C. The high concentration of GAP-43 in the growth cones may necessitate its increased synthesis in neurons with elongating axons. Its location and phosphorylation by kinase C suggest that it could perform a function in the growth cone that is modulated by extracellular signals, such as those used in pathfinding or in the control of axonal elongation.

Animals↗
PubMed1988

Schwann cell surfaces but not extracellular matrix organized by Schwann cells support neurite outgrowth from embryonic rat retina.

Despite evidence that glial cell surfaces and components of the extracellular matrix (ECM) support neurite outgrowth in many culture systems, the relative contributions of these factors have rarely been compared directly. Specifically, it remains to be determined which components of peripheral nerve support growth of central nerve fibers. We have directly compared neurite outgrowth from embryonic day 15 rat retinal explants placed onto beds of (1) Schwann cells without ECM, (2) Schwann cells expressing ECM (including a basal lamina), (3) cell-free ECM prepared from neuron-Schwann cell cultures, (4) nonglial cells (fibroblasts), and (5) 2 isolated ECM components, laminin and type I collagen. From the first day in culture, retinal explants extended neurites when placed on Schwann cells without ECM. Outgrowth on Schwann cells expressing ECM was also extensive, but not obviously different form that on Schwann cells alone. Ultrastructural study revealed that 95% of retinal neurites in ECM-containing cultures contacted other neurites and Schwann cell surfaces exclusively. On cell-free ECM prepared from neuron-Schwann cell cultures, neurite extension was poor to nonexistent. No neurite outgrowth occurred on fibroblasts. Retinal explants also failed to extend neurites onto purified laminin and ammoniated type I collagen substrata; however, growth was rapid and extensive on air-dried type I collagen. In cultures containing islands of air-dried type I collagen on a laminin-coated coverslip, retinal explants attached and extended neurites on collagen, but these neurites did not extend off the island onto the laminin substratum. We conclude from these experiments that neurite extension from embryonic rat retina is supported by a factor found on the surface of Schwann cells and that neither organized nor isolated ECM components provide this neurite promotion. These findings are discussed in relation to possible species differences in growth requirements for retinal ganglion cell neurites and to the specificity of response of different CNS neurites to ECM substrata.

Animals↗
PubMed1986

A comparative study of muscle spindles in slow and fast neonatal muscles of normal and dystrophic mice.

Muscle spindles from the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscles of genetically dystrophic mice of the dy2J/dy2J strain were compared with age-matched normal animals at neonatal ages of 1-3 weeks according to histochemical, quantitative, and ultrastructural parameters. Intrafusal fibers in both the soleus and EDL exhibited similar regional differences in myosin ATPase activity, and conformed to those noted previously in various adult species. In distal polar regions, all nuclear bag fibers resembled extrafusal fibers of the type 1 variety, whereas in capsular zones they could be divided into two subtypes. Nuclear chain fibers possessed a staining pattern similar to type 2 extrafusal fibers, and in contrast to the bag fibers they exhibited no regional variations. These features were consistently observed in both the normal and dystrophic muscles at all ages. Spindles varied only slightly in their number and distribution in the two types of muscle, and their location followed the neurovascular branching pattern in each. Irrespective of age or genotype, spindles in the soleus were more homogeneously dispersed, but those in the EDL were concentrated along the dorsal aspect of the muscle. No significant differences were noted in the total number of spindles between normal and dystrophic muscles. In addition, no dramatic differences were observed in the muscle spindle index for soleus and EDL. The first obvious disease-related changes were noted in extrafusal fibers of the soleus of 3-week-old mice, and spindles were often located close to these areas of fiber degeneration. Despite alterations in the surrounding tissue, however, spindles appeared morphologically unaltered in dystrophy. These observations indicate that intrafusal fibers of spindles in neonatal mice appear enzymatically and histologically unaffected in incipient stages of progressive muscular dystrophy.

Adenosine Triphosphatases↗
PubMed1986

Variation in content and function of non-neuronal cells in the outgrowth of sympathetic ganglia from embryos of differing age.

Studies on cellular interactions in the developing nervous system are greatly facilitated by the availability of tissue culture preparations that contain single or combined populations of neurons and non-neuronal cells (NNCs). Using superior cervical ganglia (SCG) from early E15 rats on air-dried collagen, we were able to prepare cultures containing neurons along with Schwann cells (SCs) as the only NNC type present without the use of antimitotic treatment and cultures containing only neurons, following brief antimitotic treatment. Light-microscopic observation of E15 outgrowth showed a uniform population of flattened cells, unlike that of E20 cultures, which contained a mixture of spindle-shaped and flattened cells. Autoradiograms following [3H]thymidine administration to E15 cultures revealed a striking gradient of nuclear labeling: Only a few cells were labeled near the explant and nearly all cells were labeled at the growth front. This was in marked contrast to E20 cultures, in which nuclei were labeled throughout the outgrowth. The conclusion that the labeling gradient is explained by the presence of SCs without other NNC types in E15 cultures was confirmed by immunocytochemical studies. Anti-laminin antibodies stain only those extracellular matrix components related to the SC surface, whereas anti-fibronectin antibodies stain fibroblast-related components (Cornbrooks et al., 1983a). Anti-laminin antibodies stained cell surfaces in both E15 and E20 outgrowth. E15 outgrowth did not stain with anti-fibronectin antibodies although marked staining was obtained in E20 cultures. Electron microscopy confirmed the presence of only SCs in E15, and of both SCs and fibroblasts in E20 outgrowth. Thus, it appears that there is a narrow developmental window in which the ganglia contain neurons and SCs but relatively few fibroblast components; cultures prepared from ganglia at this stage form outgrowth containing only neurites and SCs without antimitotic treatment. Surprisingly, neither SC ensheathment nor SC basal lamina formation was normal in E15 and E20 outgrowth. When either E15 or E20 SCG SCs were transplanted onto dorsal root ganglion neurons free of endogenous SCs, however, the sensory neurites were typically ensheathed or myelinated and basal lamina appeared 9 d later, identifying the SCG NNCs as functionally competent SCs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

A quantitative study of growth cone filopodial extension.

The extension of filopodia from growth cones of regenerating neurites from rat superior cervical ganglion neurons in tissue culture was studied. Cultures were grown on a thin layer of fibrous collagen and maintained in a medium containing serum and nerve growth factor. Time-lapse cinematography and computer-assisted morphometry were used to observe and measure the kinetics of extension of individual filopodia. Filopodia extended from the growth cone margin, trailing neurite, or from each other. Frequently, extension was preceded by the appearance at the cone margin of a nodule of cytoplasm which appeared dense in phase-contrast optics. Branch points between adjacent extending filopodia remained fixed with respect to the growth cone while the filopodia lengthened. The rate of extension was maximum just after initiation (0.12 +/- 0.4 micron/sec; mean +/- SD; n = 36) and declined thereafter until the filopodium collapsed. This initial rate of extension was directly correlated with the eventual length of the filopodium (r = 0.67). Filopodia of growth cones arising from embryonic neurons exhibited higher initial extension rates (range: 0.07 to 0.20 micron/sec; mean = 0.13 micron/sec) than those of postnatal neurons (range: 0.01 to 0.13 micron/sec; mean = 0.09 micron/sec). These data are discussed in relation to a model proposed by Tilney and Inoue [1982] for the extension, by distal addition of G-actin to growing filaments, of another type of elongating process filled with microfilaments, the acrosomal process of Thyone sperm.

Animals↗
PubMed1985

Rapid changes in synaptic vesicle cytochemistry after depolarization of cultured cholinergic sympathetic neurons.

Sympathetic neurons taken from rat superior cervical ganglia and grown in culture acquire cholinergic function under certain conditions. These cholinergic sympathetic neurons, however, retain a number of adrenergic properties, including the enzymes involved in the synthesis of norepinephrine (NE) and the storage of measurable amounts of NE. These neurons also retain a high affinity uptake system for NE; despite this, the majority of the synaptic vesicles remain clear even after incubation in catecholamines. The present study shows, however, that if these neurons are depolarized before incubation in catecholamine, the synaptic vesicles acquire dense cores indicative of amine storage. These manipulations are successful when cholinergic function is induced with either a medium that contains human placental serum and embryo extract or with heart-conditioned medium, and when the catecholamine is either NE or 5-hydroxydopamine. In some experiments, neurons are grown at low densities and shown to have cholinergic function by electrophysiological criteria. After incubation in NE, only 6% of the synaptic vesicles have dense cores. In contrast, similar neurons depolarized (80 mM K+) before incubation in catecholamine contain 82% dense-cored vesicles. These results are confirmed in network cultures where the percentage of dense-cored vesicles is increased 2.5 to 6.5 times by depolarizing the neurons before incubation with catecholamine. In both single neurons and in network cultures, the vesicle reloading is inhibited by reducing vesicle release during depolarization with an increased Mg++/Ca++ ratio or by blocking NE uptake either at the plasma membrane (desipramine) or at the vesicle membrane (reserpine). In addition, choline appears to play a competitive role because its presence during incubation in NE or after reloading results in decreased numbers of dense-cored vesicles. We conclude that the depolarization step preceding catecholamine incubation acts to empty the vesicles of acetylcholine, thus allowing them to reload with catecholamine. These data also suggest that the same vesicles may contain both neurotransmitters simultaneously.

Acetylcholine↗