Biomedical subjects
Publications and source records attributed to S Morrison.
Spin-lattice (T1) and spin-spin (T2) magnetic resonance relaxation times were examined in frontal, temporal, and striatal regions of 24 patients with schizophrenia and 10 normal comparison subjects. The schizophrenic patients had more prolonged T2 values than did the comparison subjects, particularly in the left temporal cortex and white matter, suggesting tissue pathology.
Six experiments were carried out to compare go/no-go and choice paradigms for studying the effects of intradimensional discrimination training on subsequent measures of stimulus generalization in human subjects. Specifically, the purpose was to compare the two paradigms as means of investigating generalization gradient forms and frame of reference effects. In Experiment 1, the stimulus dimension was visual intensity (brightness); in Experiment 2, it was line orientation (line-angle stimuli). After learning to respond (or to respond "right") to stimulus value (SV) 4 and not to respond (or to respond "left") to SV2 (in Experiment 1) or SV1 (in Experiment 2), the subjects were tested for generalization (recognition) with an asymmetrical set of values ranging from SV1 to SV11. Go/no-go training produced peaked gradients, whereas choice training produced sigmoid gradients. The asymmetrical testing resulted in a gradual shift of the peak of responding (go/no-go group) or in the point of subjective indifference (PSI; choice group) toward the central value of the test series; thus, both paradigms revealed a frame of reference effect. The results were comparable for the quantitative (intensity) and the qualitative (line-angle) stimulus dimensions. Experiment 3 compared the go/no-go procedure with a yes/no procedure in which subjects responded "right" to SV4 and "left" to all other intensities and found no differences between these procedures. Thus the difference in gradient forms in go/no as opposed to (traditional) choice paradigms depends on whether one or two target stimuli are used in training. In Experiment 4, in which visual intensity was used, the shift in the PSI following choice training varied positively with the range of asymmetrical test stimuli employed. In Experiment 5, also with visual intensity, the magnitude of the peak shift following go/no-go training varied as a function of overrepresenting a high or a low stimulus value during generalization testing. Experiment 6, with line angles, showed that the PSI following choice training varies in a similar way. The frame of reference effects obtained in these experiments are consistent with an adaptation-level model.
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PET examinations using L-18F-DOPA were performed on 14 patients with Parkinsonism-plus syndromes (PPLUS). A rate constant Ki was calculated by a graphical method using an arterial input function. Sequential PET images were obtained and no specific activity was measured both in cortical and cerebellar background regions. These results were compared with those in 20 normal controls and tested for intra- and interobserver variability. All patients with PPLUS showed reduced Ki values with a mean of 0.154 (ml/striatum/min), whereas controls exhibited Ki values with a mean of 0.690 (ml/striatum/min) using cortical background regions. The correlation coefficient was calculated to be r = 0.973 for the intraobserver variability and r = 0.879 for the interobserver variability in controls, and r = 0.989 or = 0.973 in PPLUS, resp. There was no significant difference in the Ki values for cortical and cerebellar background regions (p = 0.1). PET examinations using L-18F-DOPA can reliably assess the extent of nigrostriatal degeneration in vivo. Since this radiotracer binds irreversibly within the striatum PET examinations allow the quantification of a disturbed dopaminergic function which is observer-independent.
Wallerian degeneration is markedly retarded in C57BL/6/Ola mice, the majority of axons remaining intact for up to 10 days after sciatic transections. By 5 days after axotomy in normal mice P0 mRNA is markedly down-regulated, whereas high expression is present in the mutant mice at 7 days and is not reduced by a second distal axotomy. However, dissociated Schwann cells cultured without neurons down-regulate P0 in the normal manner. The data suggest that the continued expression of P0 mRNA is probably dependent on a relatively stable axonal signal with a low turnover that does not require continuous fast anterograde or retrograde transport. This may indicate an intrinsic axolemmal molecule(s) is involved in the neuronal signal.
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This study examines the expression of the major myelin protein gene P0 in cultured Schwann cells, grown on their own or in association with neurons. Many freshly dissociated Schwann cells from actively myelinating nerves express Po mRNA in high abundance. If neurons are not present, signal intensity falls markedly with time so that by 7 days in culture only a basal expression is evident which is negligible compared to the level in vivo. Dorsal root ganglia from embryo day 16 (E16) rats contain no significant levels of Po mRNA but when grown in full myelinating medium (containing serum and embryo extract) increasing expression is seen from 4 to 5 days onward even though myelination does not occur until after the second week. In this intervening period the intensity of P0 mRNA expression is lower than that found in the actively myelinating cell. Neurons from sympathetic ganglia are also capable of inducing P0 mRNA expression. Schwann cells in dorsal root ganglia explants grown in serum-free defined medium do not assemble a basal lamina and will not wrap or myelinate axons. Nevertheless P0 mRNA, but not protein, is expressed in levels similar to those found in full myelinating medium prior to myelination. Such Schwann cells also exhibit galactocerebroside and the sulphatide recognised by the 04 antibody. It appears that in defined medium or in myelinating medium prior to myelination axonal signals can induce P0 mRNA expression to a certain degree. However, full up-regulation is usually associated with the rapid membrane expansion accompanying myelination. Whether this augmented up-regulation is due to further axonal signalling or events in the Schwann cell is unknown, but the results suggest that P0 expression can be regulated at several stages of synthesis.
In Experiment 1, 2 groups of human subjects were trained to respond to 1 of 2 light intensity stimuli, S2 or S4, and then were tested for generalization with a randomized series of increasing values from S1 to S11. Both groups, including the group trained to respond to dimmer value, showed peak shifts to a brighter more centrally located test stimulus. In Experiment 2, which used line angle stimuli, both the size of the difference between S+ and S- and the range of test stimuli that extended beyond S+ were varied. The larger the S(+)-S- separation and the larger the range, the greater was the peak shift obtained. In Experiment 3, training involved an S- (line angle) surrounded by 2 S+ values with testing symmetrical about the training values and covering either a narrow or a wide range. The wide range produced greater peak shifts in both directions from S-. All 3 experiments support an adaptation-level interpretation of intradimensional discrimination learning and generalization test performance in human subjects. Related work with animals suggests the presence of similar processes.
Among 24 chronic schizophrenic patients, the 10 with high ratings for negative symptoms had significantly higher left-frontal: temporal-cortical T2 ratios. This finding was unrelated to age, dose of medication, length of illness or handedness. No T1 or T2 changes were found to be associated with positive symptoms or tardive dyskinesia in the regions examined.
Recombination-dependent alterations of their expressed pilin gene (pilE) enable gonococci to synthesize a myriad of structurally/antigenically different pili and to reversibly switch their pilus production on and off. These changes have been ascribed both to DNA transformation and to intragenomic recombination between pilE and silent pilin genes (pilS). We examined the pilus changes in gonococci that are incompetent for transformation because of their DNA uptake deficiency (dud) mutation, pilus- (P-) phenotype, or both. Though incompetent for DNA transformation, dud cells displayed pilus antigenic variation and underwent reversible pilus variations much like their wild-type parent. Wild-type P- with a pilE nonsense mutation were also virtually nontransformable, but they reverted to P+ at high frequencies. The pilin mRNA sequence changes that accompanied pilus transitions in these nontransformable dud and P- gonococci represent insertion of pilS stretches into their respective pilE, apparently via intragenomic recombination.
We obtained a topographic computer analysis of the electroencephalogram in 53 normal elderly subjects. Normal aging was not associated with an increase in slow (delta) activity. However, cognitive performance correlated positively with fast (beta) activity particularly in frontal leads, even after controlling for age, education, occupation, and medication. Five subjects who showed early signs of cognitive decline, had all a marked reduction in beta activity suggesting that this may be an early indication of intellectual loss.
The expression of many myelin-specific molecules in Schwann cells is profoundly decreased following denervation. This study examines the early reexpression of myelin protein genes associated with reinnervation. Following sciatic nerve crush, the distal, regenerated nerve was divided into appropriate (2.5 or 5 mm) consecutive lengths in which gene expression was monitored using Northern blotting, in situ hybridization, and immunostaining. The spatial separation of the distal axon tip and the more proximally located Schwann cells showing initial upregulation of P0 mRNA was constant over the period of 5-13 days after crush at approximately 3-4 mm in fixed, processed material. Axons associated with Schwann cells showing the initial upregulation were completely or partially enveloped in Schwann cell cytoplasm, with very few having any degree of ensheathment. It is probable that only a limited axon-Schwann cell contact is required for induction of the myelin protein genes. Myelin-associated glycoprotein mRNA was upregulated prior to those for P0 and myelin basic protein which had similar time courses. Reexpression of galactocerebroside also preceded that for P0 mRNA. Signal abundance for all myelin proteins decreased in a proximal to distal direction from the crush site, and with time the "wave" of upregulation moved distally down the nerve. In the more proximal, remyelinating zones, the signal intensity exceeded that of the contralateral normal nerve. Signal intensity also varied considerably between adjacent, expressing Schwann cells. The data provide further evidence of the strong temporospatial relationship between axons and the regulation of myelin protein genes in Schwann cells.
The effect of optic nerve transection on myelin protein gene expression was studied in rats following axotomy at two ages: during active myelination (17 days of age) and after peak expression of the genes (35 days of age). mRNA levels for proteolipid protein, myelin basic protein and myelin-associated glycoprotein were assessed by northern and dot blotting and by in situ hybridization using tissue sections and cultured individual oligodendrocytes. Transection at 17 days caused down-regulation of mRNAs for proteolipid protein, myelin basic protein and myelin-associated glycoprotein by 5 days after axotomy with an increase in GFAP mRNA. A more protracted change followed axotomy at 35 days of age. The abundance of mRNAs for proteolipid protein and myelin basic protein was significantly reduced by 28 days after transection in the affected nerve. Quantification of proteolipid protein mRNA expression in individual oligodendrocytes confirmed the down-regulation. However, in contrast to the effects on the major myelin proteins, the abundance of myelin-associated glycoprotein mRNA increased in the affected nerve for at least the initial month after lesioning at 35 days. The results show that optic nerve transection has significant effects on myelin protein mRNA expression in oligodendrocytes of optic nerve. However, the changes in myelin protein gene activity are relatively small and more protracted than those seen in Schwann cells after peripheral nerve section. Because axotomy also causes marked changes in the glial population of the optic nerve it is not possible unequivocally to ascribe the alteration in gene expression to loss of axons. However, the data may provide evidence that axons do influence myelin protein genes in oligodendrocytes and are necessary for them to develop their full expression.
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Kaposi's sarcoma has only rarely been reported in children with acquired immunodeficiency syndrome. In contrast to adult patients, in whom the disease is predominantly cutaneous, among pediatric patients with acquired immunodeficiency syndrome, Kaposi's sarcoma is primarily limited to the lymphadenopathic form. We describe two children with the acquired immunodeficiency syndrome who developed diffuse nodular skin lesions of Kaposi's sarcoma.
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The expression of myelin protein genes in Schwann cells has been studied in situ hybridization. 35S-UTP-labelled, antisense and sense RNA probes to the major protein Po, myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and proteolipid protein (PLP) were employed with paraffin-embedded sections, teased fibres and dissociated Schwann cells from sciatic nerves of rats. Teased fibres were also prepared from cervical sympathetic trunks. Po mRNA was strongly expressed in the mid-internodal perinuclear area of Schwann cell cytoplasm. The degree of signal appeared to be related to fibre size. MBP mRNA showed a diffuse pattern along the Schwann cell internode with a marked increase in grains at the paranodal cytoplasm, particularly in larger fibres. This distribution suggests that the paranodal area is a major site of insertion of MBP into myelin membrane. The expression of MAG and PLP mRNA was markedly lower than Po and MBP. Both mRNAs were localized in the perinuclear cytoplasm and showed a dependence on fibre size. No significant signal was present in Schwann cells associated with unmyelinated axons. In addition to providing data on the cellular expression of myelin protein genes, these studies have shown that teased fibres are invaluable in allowing the localization of low abundance mRNAs.
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