PubMed Health⌕ Search

Biomedical subjects

L Charron

Publications and source records attributed to L Charron.

At least 19 recordsLinked to original sources

6p24-22 region and major psychoses in the Eastern Quebec population. Le Groupe IREP.

Recent reports of a linkage trend in 6p24-22 for schizophrenia (SZ), in different samples, were tempered by the concurrent evidence of negative reports in other samples. In the studies showing positive results, different definitions of affection and a wide spectrum of diagnoses were used. Our objectives were not only to test for linkage at 6p24-22 in the Eastern Quebec population, but also to test whether this putative vulnerability locus was either selectively linked to schizophrenia (SZ), or to bipolar disorder (BP), or to both major psychoses. Parametric and nonparametric linkage analyses with 12 microsatellite markers in 6p24-p22 were performed on a sample of 18 large multigenerational pedigrees (N = 354) either affected by SZ, or by BP, or equally affected by both major psychoses (i.e., mixed pedigrees). Three affection definitions were usually tested in our program: one on schizophrenia (SZ), one on bipolar disorder (BP), and one that comprised SZ and BP under the hypothesis of a susceptibility locus common to both in major psychoses (common locus, CL). The results of parametric analyses did not support a major gene hypothesis. However, in one large mixed pedigree (#151), we observed with the common locus phenotype (CL) lod scores of 2.49 and 2.15, respectively, at the D6S296 and D6S277 loci under a dominant model. Our data suggest the presence of a potential vulnerability locus at 6p24-22 that could be related to both schizophrenia and bipolar affective disorder. These results may be seen as congruent with former studies that used schizoaffective as well as schizophrenia diagnoses as entry criteria for the affected families, and used an affection definition that comprised affective psychoses as well as schizophrenia.

Bipolar Disorder↗

Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure.

OBJECTIVE: The reliability and accuracy of the best-estimate diagnostic procedure were examined, and factors associated with reliability were determined. METHOD: The subjects were 134 members of large multigenerational pedigrees densely affected by bipolar disorders or schizophrenia. Three best-estimate diagnoses were derived: first, by a research psychiatrist and research assistant unblind to the relatives' diagnoses; second, by two blind independent psychiatrists; third, by a panel of four blind psychiatrists. The subjects were characterized on several clinical and methodological variables, which were used to compare the agreements of two types of best-estimate diagnoses with the disagreements. RESULTS: There was satisfactory agreement between the unblind and blind consensus best-estimate diagnoses and between the two blind independent psychiatrists. Latent class analyses revealed that limited sensitivity was the main source of imperfect reliability. Confusability analyses revealed that the most problematic diagnostic distinctions involved schizoaffective disorder, which was confused with schizophrenia, bipolar I disorder, and schizophreniform disorder. Blindness significantly affected diagnostic outcome in latent class analyses. Moreover, for diagnostic disagreements, unblind diagnoses had greater continuity with the most predominant diagnosis in the pedigree than did blind diagnoses. Diagnostic disagreements were associated with the presence of mixed affective and psychotic symptoms, less diagnostic certainty, and shorter duration of illness. CONCLUSIONS: These results suggest that it is possible to identify cases that are more likely to lead to diagnostic disagreements in family and epidemiological studies and that blind diagnoses may help to prevent false positive diagnoses, which may be particularly detrimental to genetic linkage analyses.

Adult↗

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: Postnegative distinction and childhood predictors of adult outcome.

BACKGROUND: The aim of this study was to verify the presence and stability across life of the positive/negative distinction in early-onset schizophrenia (EO-SZ) through a longitudinal factor analysis of the schizophrenic dimensions, and to identify the factors predicting several indices of long-term outcome for EO-SZ. METHOD: Forty children consecutively referred for DSM-III-R schizophrenia (SZ) in a specific catchment area comprised the sample. RESULTS: Across a 14.8-year follow-up, longitudinal factor analysis identified two separate factors corresponding to the positive and negative symptom dimensions. We also observed that: the GAS rated over the last three years of adult illness and the severity of negative symptoms during the stabilised interepisode intervals in adulthood were the indices of adult outcome that were most easily predicted; and the best childhood predictors of adult outcome were premorbid functioning and severity of positive and negative symptoms during acute episodes. CONCLUSIONS: The presence of premorbid non-psychotic behaviour disturbances (NPBD) and premorbid developmental problems was not related to severity of outcome, in contrast to the former variables.

Adolescent↗

Three-dimensional computer-aided analysis of the intraganglionic topography of primary muscle afferent neurons in the rat.

A microcomputer system was used to reconstruct, in the L5 dorsal root ganglion (DRG) of the rat, the three-dimensional arrangement of primary neurons which had been labelled by application of horseradish peroxidase (HRP) and fluoro-gold (FG) to various muscle nerves of the leg. Analysis of the data and animation of the reconstructed images with commercially available software were instrumental in identifying the preferential intraganglionic locations of the neurons innervating muscles such as the soleus (SOL), the gastrocnemius lateralis (GL), and medialis (GM), or parts of the GM. These locations appeared to be somewhat related to the position of the muscles in the posterior compartment of the leg. Additionally, the study provided quantitative estimates of muscle afferent neuronal populations, allowed a comparison of the labelling performances of HRP and FG, and finally indicated that few DRG neurons project to two different muscles.

Animals↗

Changes in lectin binding of lumbar dorsal root ganglia neurons and peripheral axons after sciatic and spinal nerve injury in the rat.

The effects of chronic lesions of rat lumbar spinal or sciatic nerves on the binding of Glycine max (soybean) agglutinin to galacto-conjugates, in small- and medium-size primary sensory neurons of the L4 and L5 dorsal root ganglia, were examined over a 580-day period. Spinal nerve section resulted in a marked decrease in the population of stained neurons within 7 days. However, despite some retrograde morphological changes triggered by axonal injury, the proportion of stained nerve cells was normalized 180 days postoperatively. This temporary decrease in perikaryal lectin reactivity was initially associated with a marked accumulation of stained material in the nerve, proximal and distal to the site of section, with similar accumulations also being noticeable at each level of injury in sciatic nerves subjected to double ligature. This may reflect the presence of glycocompounds linked to the autolysis of nerve fibers during the phase of retrograde dying-back and Wallerian degeneration. At later stages, stained deposits could be seen scattered along central and peripheral axonal processes of the dorsal root ganglion neurons in the vicinity of the cell body. They may indicate a disturbance in the peripheral turnover of glycoproteins in chronically-transected nerves, with piling up of neuronal products. Sciatic nerve injury caused similar but less severe effects which, except for the L4 ganglion cells, were rapidly reversible.

Animals↗

A comparative study of the effects of chronic axotomy, crush lesion and re-anastomosis of the rat sural nerve on horseradish peroxidase labelling of primary sensory neurons.

Chronic axotomy is detrimental to the incorporation of horseradish peroxidase (HRP) by neurons of the central and peripheral nervous system. Using the rat sural nerve as a model, this study aimed to determine the effects of other types of nerve injury on the peroxidase labelling of dorsal root ganglion (DRG) cells. Compared to the decreased labelling occurring shortly after permanent transection of the sural axons at the ankle, crush injury of the nerve had no effect on the number and size distribution of peroxidase-stained cells. Re-anastomosing the sural nerve to its own distal segment or to the tibial nerve delayed the changes in HRP neuronal labelling, which subsequently were less severe in neurons allowed to reinnervate their own nerve. It also sustained the incorporation of HRP by many large DRG neurons, a function which is lost shortly after these cells are chronically axotomized. Nerve re-anastomosis also prevented the retrograde atrophy of myelinated and unmyelinated nerve fibers which is triggered by permanent transection. Based on the preservation of fiber counts in the sural nerves proximal to the site of surgery, with no evidence of degeneration, our observations possibly reflect alterations in the peroxidase metabolism of DRG neurons depending on the type of axonal injury they sustained and the possibility they had upon regeneration to contact endoneurial tubes and ultimately their original end-organs.

Animals↗

Carbonic anhydrase and horseradish peroxidase: double labelling of rat dorsal root ganglion neurons innervating motor and sensory peripheral nerves.

Dorsal root ganglion neurons supplying peroneus longus, soleus and gastrocnemius medius muscles and the sural nerve of the rat were labelled with horseradish peroxidase and analysed for their carbonic anhydrase content. Staining of the sections was done either on the same or on alternate slides. Both methods led to the same results, despite a slight fading of the carbonic anhydrase reaction in double-stained sections. The data indicated that the muscles under study were supplied by approximately the same number of horseradish peroxidase-labelled cells, irrespective of their differences in size. 74.9% of these labelled neurons had diameters exceeding 30 microns and 52.4% of them also stained for carbonic anhydrase. The double-labelled cells represented 66.9% of the population of large neurons (greater than 30 microns) and comprised most of those measuring over 47.5 microns. Richness in carbonic anhydrase of the large muscle afferent neurons may be linked to their innervation of the stretch receptors, as components of an active apparatus which includes the gamma motor axons which also stain positively for carbonic anhydrase. In contrast, the ganglion cells supplying the sural nerve were almost totally devoid of carbonic anhydrase, as only 6.4% showed double labelling. This contingent possibly represents the muscle afferents of the small motoneural population which supplies, through this nerve, part of the foot musculature of the rat.

Acid-Base Equilibrium↗

Differences in horseradish peroxidase labeling of sensory, motor and sympathetic neurons following chronic axotomy of the rat sural nerve.

In an attempt to clarify the ultimate fate of permanently axotomized adult primary neurons, horseradish peroxidase (HRP) was used as a cell marker to label the motor, sensory and postganglionic sympathetic neurons of rat sural nerves which had been sectioned at the ankle and prevented from regenerating for periods of up to 80 weeks. Axotomy did not affect sympathetic neurons, but resulted 4 weeks later in a sudden reduction in the number of labeled sensory and motor cells which persisted to the end of the study. The missing neuronal population amounted to 44.4% and 45.9% respectively of the normal sensory and motor contingent and included most of the large afferent and efferent neurons. However, examination of sural nerves at the thigh, 30 mm proximal to the neuroma, revealed marked axonal atrophy but no change in the number of myelinated and unmyelinated fibers up to 52 weeks after axotomy. Such prolonged survival of the peripheral processes is indirect evidence that axotomized neurons can endure long-term detachment from their end organs and suggests that the lack of HRP labeling in certain sensory and motor neurons does not imply their degeneration, but expresses one of many retrograde dysfunctions triggered by axotomy.

Animals↗

Carbonic anhydrase activity in the normal and injured peripheral nervous system of the rat.

The carbonic anhydrase reactivity of primary neurons and axons of the L4 and L5 lumbar levels was studied in rats before and after various surgical procedures including transection of the spinal cord, removal of dorsal root ganglia, and transection of ventral or dorsal roots or spinal nerves. In normal animals, carbonic anhydrase reactivity was confined to large and medium size neurons of the dorsal root ganglia, and was also present in a sizeable percentage of cells scattered throughout the thoracolumbar sympathetic chain and in the celiac ganglion. At root level, enzymatic staining could be detected in 48.7% of the dorsal root myelinated axons of most sizes, whereas in ventral roots, it was restricted to small myelinated axons, in a proportion much higher at the L4 than in the L5 level. Spinal motoneurons remained unlabeled, despite procedures aimed at increasing the somal concentration of carbonic anhydrase, such as ventral root ligation and blocking of the fast or slow axoplasmic transport using colchicine or iminodiproprionitrile. However, it is likely that reactive ventral root axons originate from neurons situated segmentally in the spinal cord, and do not constitute aberrant sensory fibers, as carbonic anhydrase activity remained unchanged in the L4 and L5 ventral roots after removal of the corresponding spinal ganglia, whereas it disappeared after damage to the spinal cord at the lumbar level, or at a site distal to a ventral root section. Enzymatic staining of neurons of the dorsal root ganglia was not modified by a dorsal rhizotomy, but showed a marked decrease after transection of the spinal nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Decreased horseradish peroxidase labeling in deafferented spinal motoneurons of the rat.

It has been suggested that the incorporation and retrograde transport of horseradish peroxidase (HRP) were linked to the level of neuronal activity. Therefore one could postulate that the motor impairment resulting from dorsal rhizotomy affects the HRP labeling of spinal motoneurons in the absence of morphological damage to the motor system. This hypothesis was tested in the adult rat by sectioning bilaterally the L3-L5 dorsal roots. 2-18 months after surgery, the L4 radicular nerve was immersed in a solution of HRP. Labeled motoneurons were counted together with the motor axons of the L4 ventral root and results were compared with values obtained in paired controls. Deafferentation resulted in a crippling deficit of lower limb movements with disuse atrophy of muscle fibers but had no effect on the fiber population of the sciatic nerve and the L4 ventral root. Whereas in normal animals the L4 HRP-labeled motoneurons represented 71.9-98.3% (average 85.4) of the motor axonal counts, in animals studied 4, 12 and 18 months after dorsal rhizotomy, the number of motoneurons containing HRP granules constituted only 20.1-55.7% (average 46.2) of the number of motor axons and many of the labeled cells were faintly stained. These findings, which may reflect either a decreased retrograde transport of HRP in deafferented motoneurons or an increased turnover of the enzyme in the cell body, call attention to the possibility that the degree of activity in neuronal pathways influences HRP labeling.

Afferent Pathways↗

Motoneuronal and motor axonal innervation in the rat hindlimb: a comparative study using horseradish peroxidase.

In order to validate the horseradish peroxidase (HRP) technique as a quantitative method for assessing neuronal pools, we compared counts of labeled motoneurons to numbers of corresponding motor axons. Rat spinal motoneurons were labeled by immersing in HRP either the L4 radicular nerve or the normal or deafferented nerve to the tibialis anterior muscle (TA). The technique slightly under-valued the L4 motoneuronal population estimated by counting ventral root motor fibres, while in deafferented TA, counts of labeled neurons closely reflected numbers of motor axons. Measurements of neuron and nerve fibre diameters revealed good correlations of alpha and gamma motor estimates at spinal cord and nerve levels. Values were considered representative because of the approximation obtained in HRP-estimates between control and deafferented animals, indicating no significant damage from the surgical deafferentation.

Animals↗

Type I fiber atrophy and internal nuclei. A form of centronuclear myopathy?

A 6-year-old boy had a myopathy characterized by central nuclei with type I muscle fiber atrophy and preponderance. Study of the family members demonstrated no abnormalities with the exception of an unusually high incidence of centrally located muclei in the muscle biopsy specimen of the mother. A review of the literature disclosed a limited number of cases with identical morphological abnormalities, suggesting that they constitute a form of centronuclear myopathy with some distinctive clinical features.

Adenosine Triphosphatases↗

Motor and sensory neurons of the rat sural nerve: a horseradish peroxidase study.

Neurons of origin of the rat sural nerve were labelled with horseradish peroxidase. Dorsal root ganglionic cells were located in the L4 and L5 ganglia, and occasionally at the L6 level. Most of these sensory neurons measured under 35 microns in diameter. In keeping with previous electrophysiological studies suggesting the presence of motor fibers to plantar muscles in the rat sural nerve, motoneurons were identified at the caudal end of the L5 spinal segment, intermingled in the posterior aspect of the ventral horn with posterior tibial motor cells supplying the foot muscles. A quantitative analysis of HRP-labelled motoneurons revealed no difference between normal (average 67) and deafferented animals (average 70), the values being only marginally lower than counts of motor axons in deafferented sural nerves (average 80).

Afferent Pathways↗

Vasculitic neuropathy in rheumatoid disease and Sjögren syndrome.

Two patients with rheumatoid arthritis and one with Sjögren syndrome had a severe sensorimotor neuropathy preceding or up to 5 years after the onset of the disease. Electrophysiologic and sural nerve biopsy studies revealed an axonal neuropathy. Myelinated fibers were affected to a greater extent than unmyelinated axons. Peripheral nerve damage was related to occlusion of the vasa nervorum, since vasculitic involvement of epineurial vessels was observed in all patients. Despite the severity of the neuropathy, it may recover, because, compared with axons, Schwann cells are perhaps less vulnerable to ischemia.

Action Potentials↗

Sensory neuropathy associated with primary biliary cirrhosis. Histologic and morphometric studies.

Sensory symptoms can develop in the course of primary biliary cirrhosis. They have been attributed to xanthomatous infiltrates of the nerves. We report a case of a young woman suffering from pure sensory neuropathy starting at a time when evidence of liver disease was minimal. Histologic and morphometric studies of sural nerve biopsy specimens obtained from calf and ankle showed a dying-back type of axonal degeneration predominantly affecting large myelinated fibers. No lipid-containing cells were seen, which raises the possibility that other mechanisms related to primary biliary cirrhosis are involved in the pathogenesis of the neuropathy.

Adult↗

Neuropathy and mitochondrial myopathy.

It has been stated that peripheral neuropathy can be a feature of so-called ophthalmoplegia-plus syndrome, but to date only one case of hypertrophic neuropathy has been reported. This study is concerned with the clinical, electrophysiological, and pathological observations in a 37-year-old man with progressive external ophthalmoplegia and a ragged-red fiber myopathy associated with severe sensorimotor neuropathy. Histological and morphometric studies of the sural nerve revealed a marked loss of large myelinated fibers and an occasional degenerating axon. Residual fibers had disproportionately thin myelin sheaths in relation to axon calibers. In contrast to the muscle biopsy findings, no mitochondrial paracrystalline inclusions were observed in the nerve. However, the number of mitochondria per square micron of Schwann cell cytoplasm was elevated when compared with values obtained from normal subjects and a patient with a chronic neuropathy. These findings may indicate an alteration of mitochondrial function common to muscle fibers and Schwann cells which, in nerves, could lead to axon loss and abnormality of myelination.

Humans↗

The neuropathy of Charlevoix-Saguenay ataxia: an electrophysiological and pathological study.

Two female patients aged 30 and 40 years with the Charlevoix-Saguenay ataxia were studied. Both had absent sensory action potentials in upper and lower extremities but, unlike typical cases of Friedreich's ataxia, they displayed a marked slowing of motor conduction velocities. Sural nerve biopsies taken from calf and ankle revealed a severe loss of large myelinated axons contrasting with a normal myelinated fiber density. Evidence for active axonal degeneration was scarce, with no indication of axonal regeneration. Teased myelinated fibers revealed an increased variability of internodal length but no evidence for myelin breakdown. These findings support, as a primary defect, a developmental abnormality of peripheral nerve, namely a lack of maturation of large myelinated axons and possibly a faulty myelination of nerve fibers. We think it is unlikely to represent a progressive axonal atrophic or dystrophic process, as suggested in Friedreich's ataxia.

Action Potentials↗