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Biomedical subjects

J Armand

Publications and source records attributed to J Armand.

At least 19 recordsLinked to original sources

Functional differences in corticospinal projections from macaque primary motor cortex and supplementary motor area.

We made a quantitative comparison of the density of macaque corticospinal projections from primary motor cortex (M1) and supplementary motor area (SMA) to spinal motor nuclei supplying hand and finger muscles. We also compared the action of corticospinal outputs from these two areas on 84 upper limb (mostly hand) motoneurones in chloralose-anaesthetised macaques. The hand representations of M1 and SMA were first identified using MRI and intracortical microstimulation. We made focal injections of WGA-HRP into these representations. Densitometric analysis showed that corticospinal projections from M1 were far denser and occupied a much greater proportion of the hand muscle motor nuclei than did SMA projections. Stimulation of M1 and SMA with bipolar intracortical pulses evoked monosynaptic EPSPs. These were significantly larger and more common from M1 (88% of motoneurons) than from SMA (48%). The results demonstrate corticomotoneuronal connections from both M1 and SMA, some converging upon single motoneurons. Both areas give rise to CM projections but that those from M1 are far more numerous and exert stronger excitatory effects than those from the SMA.

Animals↗

Differences in the corticospinal projection from primary motor cortex and supplementary motor area to macaque upper limb motoneurons: an anatomical and electrophysiological study.

To further our understanding of the functional roles of different motor cortical areas, we made a quantitative comparison of the density of corticospinal projections from primary motor cortex (M1) and supplementary motor area (SMA) to spinal motor nuclei supplying hand and finger muscles in four macaque monkeys. We also compared the action of corticospinal outputs excited by electrical stimulation of these two areas on upper limb motoneurons recorded in three anaesthetized macaques. The hand representations of SMA and M1 were first identified using structural magnetic resonance imaging scans and intracortical microstimulation. In the anatomical study we then made focal injections of wheatgerm agglutinin- horseradish peroxidase into these representations, which were subsequently confirmed by analysis of retrograde cortical labelling. Densitometric analysis showed that corticospinal projections from M1 were denser and occupied a greater proportion of the hand muscle motor nuclei than did projections from SMA. In caudal Th1 the densest projections from M1 occupied 81% of this motoneuronal area, compared with only 6% from SMA. In the electrophysiological study, bipolar intracortical stimulation of the hand representation of M1 and SMA evoked direct (D) and indirect (I) corticospinal volleys. Volleys elicited by M1 stimulation had larger amplitudes and faster conduction velocities than those evoked from the SMA. Intracellular recordings were made from 84 contralateral upper limb motoneurons. M1 and SMA stimulation evoked markedly different responses in tested motoneurons: EPSPs were larger and more common from M1 (88% of motoneurons) than from SMA (48%). Some motoneurons (16/84) showed evidence of excitatory postsynaptic potentials mediated by monosynaptic action of the D-wave evoked from M1; these early effects were not observed from the SMA. In most motoneurons (74/84) EPSPs had segmental latencies indicating that they were due to monosynaptic action of the I-wave. The results are consistent with cortico-motoneuronal (CM) connections originating from both SMA and M1 converging upon single motoneurons, but those from M1 are far more numerous and exert stronger excitatory effects than from the SMA. Thus although they may function in parallel, the two CM projections probably make different contributions to upper limb motor control.

Animals↗

Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma.

The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.

Adult↗

Postnatal development of corticospinal projections from motor cortex to the cervical enlargement in the macaque monkey.

The postnatal development of corticospinal projections was investigated in 11 macaques by means of the anterograde transport of wheat germ agglutin-horseradish peroxidase injected into the primary motor cortex hand area. Although the fibers of the corticospinal tract reached all levels of the spinal cord white matter at birth, their penetration into the gray matter was far from complete. At birth, as in the adult, corticospinal projections were distributed to the same regions of the intermediate zone, although they showed marked increases in density during the first 5 months. The unique feature of the primate corticospinal tract, namely direct cortico-motoneuronal projections to the spinal motor nuclei innervating hand muscles, was not present to a significant extent at birth. The density of these cortico-motoneuronal projections increased rapidly during the first 5 months, followed by a protracted period extending into the second year of life. The densest corticospinal terminations occupied only 40% of the hand motor nuclei in the first thoracic segment at 1 month, 73% at 5 months, and 75.5% at 3 years. A caudo-rostral gradient of termination density within the hand motor nuclei was present throughout development and persisted into the adult. As a consequence, the more caudal the segment within the cervical enlargement, the earlier the adult pattern of projection density was reached. No transitory corticospinal projections were found. The continuous postnatal expansion of cortico-motoneuronal projections to hand motor nuclei in primates is in marked contrast to the retraction of exuberant projections that characterizes the development of other sensory and motor pathways in subprimates.

Animals↗

An electrophysiological study of the postnatal development of the corticospinal system in the macaque monkey.

Postnatal development of the corticospinal system was investigated in 13 macaques using noninvasive transcranial magnetic stimulation (TMS) of the motor cortex and direct electrical stimulation of corticospinal axons in the medullary pyramid and spinal cord. The latency of antidromic corticospinal volleys evoked from the pyramid and recorded from the motor cortex decreased dramatically during the first postnatal months. Our data predict that conduction velocity (CV) of the fastest corticospinal neurons over their cranial course would reach adult values at approximately 11 months. The CV of corticospinal neurons in the spinal cord increased with age but with a slower time course. In the neonate, the fastest spinal CV was estimated at 7.8 m/sec, approximately 10 times slower than in adults (mean 80.0 m/sec). Our data predict that full myelination of corticospinal axons in the spinal cord would not occur until approximately 36 months. No short-latency EMG responses were elicited in arm and hand muscles by TMS until 3 months of age; TMS thresholds were high initially and then fell progressively with age. When corrected for body size, relative latencies of EMG responses showed an exponential decrease during the first postnatal months. Our data are consistent with the hypothesis that fine finger movements are not observed before functional CM connections are well established and that rapid changes in the physiological properties of the corticospinal system coincide with the period in which precision grip is known to mature (3-6 months). However, corticospinal development continues long after simple measures of dexterity indicate functional maturity, and these changes may contribute to the improved speed and coordination of skilled hand tasks.

Aging↗

Acid-base balance in plasmatic, pericardial and peritoneal fluids in 2 species of amphibians.

The carbonic acid-base balance and the concentrations of Na and Cl were studied in 3 fluids, plasmatic, pericardial and peritoneal, sampled from 2 species of amphibians: Pleurodeles waltl and Xenopus laevis. In Pleurodeles the pericardial and peritoneal fluids are in a state of marked metabolic alkalosis, the carbonate alkalinity being up to 10 times higher in the serosal fluids than in the plasma, whereas PCO2's are very close in the 3 fluids. The Cl concentration is markedly lower in the serosal fluids than in the plasma. In Xenopus, the metabolic alkalosis of the serosal fluids also exists, but to a much lower extent than in Pleurodeles. These observations lead to further researches in the field of morphometry, physicochemistry and physiology.

Acid-Base Equilibrium↗

Prolonged elevation of intracellular cyclic AMP levels in U937 cells increases the number of receptors for and the responses to formylmethionyl-leucylphenylalanine, independently of the differentiation process.

The effects of elevated levels of cyclic AMP induced by cholera toxin (CTx) were investigated on the differentiated promyelomonocytic cell line U937. After CTx treatment, the initial inhibition of the oxidative burst induced by N-formylmethionyl-leucyl-phenylalanine (FMLP) was followed by a progressive increase over 20 h, resulting in 4-6-fold potentiation of the initial burst. Various cyclic-AMP-elevating agents produced similar potentiation of the FMLP- or C5a-induced oxidative burst, but the phorbol 12-myristate 13-acetate-induced oxidative burst was not affected by CTx pretreatment of cells. Furthermore, the increase in arachidonate release and intracellular Ca2+ triggered by FMLP were amplified after CTx treatment. ADP-ribosylation of Gi alpha subunits catalysed by pertussis toxin was slightly increased after CTx treatment, despite similar immunoreactivity of the alpha subunit of Gi2. FMLP binding sites present in CTx-treated membranes were 3-6 times more abundant than in control membranes. Expression of mRNAs encoding the FMLP receptor and one of its related receptors were enhanced after CTx treatment of both undifferentiated and undifferentiated U937 cells. In parallel, after undifferentiated cells were treated with CTx, they were able to increase intracellular Ca2+, but not the oxidative burst, in response to FMLP. These data demonstrate that CTx, by increasing cyclic AMP, enhances the expression of chemotactic receptors independently of U937 cell differentiation.

Amino Acid Sequence↗

[Rupture of an aneurysm of the internal iliac artery into the primary iliac vein].

Authors present a case of spontaneous rupture of internal iliac artery in common iliac venous, and propose a review of cases reported in literature. Abreast of modern imagery and especially computed tomography is able to give a precise diagnosis, but angiography is the Most accurate procedure for detecting arteriovenous fistula and cannot be excluded out of diagnostic approach.

Aged↗

Protracted postnatal development of corticospinal projections from the primary motor cortex to hand motoneurones in the macaque monkey.

We have studied the development of corticospinal projections from the hand area of the primary motor cortex to the spinal cord using anterograde transport of WGA-HRP. In the neonate, as in the adult, corticospinal projections to the intermediate zone at the C8/T1 spinal level were clearly present. However, in contrast to the adult, there was only very faint and barely visible labelling in the dorso-lateral motor nuclei which supply the hand muscles. No aberrant projections to other motor nuclei were seen. By 2.5 months, a ring of dense labelling was present around the dorso-lateral motor nuclei, but labelling was still sparse in the central region. This labelling was more pronounced at 11 months, but was still not as heavy as in the adult. There was no labelling among the ventral motoneurones at any age. The conduction velocity (c.v.) of the fastest corticospinal fibres was determined in each of the monkeys. There was an age-related increase in c.v. within the spinal cord. At birth, the fastest axons had a c.v. of only 8 m.s-1. At 11 months c.v. was still substantially slower (55 m.s-1) than the adult value of 73 m.s-1. In contrast, by 11 months, the axonal c.v. within the brain was close to the adult value, suggesting a rostro-caudal maturation of the corticospinal system. Our results demonstrate that corticospinal projections in the macaque monkey mature gradually over a period of at least 11 months, much longer than previously thought.

Animals↗

Optimum incubation conditions of the domestic guinea fowl egg.

1. During artificial incubation of 8000 guinea fowl eggs, the effects of temperature, relative humidity, rate of inflowing air and age of the laying flocks were determined. 2. Total duration of incubation was divided into setter (0 to 24 days) and hatcher (25 to 28 days) periods. Eggs transferred at the end of the setter period, (ET, % of fertile eggs) and hatching rate (HR, % of transferred eggs) were calculated, as well as the total hatching rate expressed as percentage of fertile eggs. 3. In the range 36 to 39 degrees C, temperature affected significantly (P < 0.001) ET and HR, with optima at 37.2 and 37.0 degrees C +/- 0.1 degrees C respectively. 4. During incubating period, relative humidity in the range 40 to 64% (water vapour partial pressure, PH2O = 17 to 34 Torr at 36 to 39 degrees C), significantly (P < 0.001) affected the total diffusive water loss and hatchling mass, both expressed as percentage of fresh egg mass. ET was significantly affected by water loss, the highest ET being for water loss of 13.3 +/- 0.5%. Optimal relative humidity was calculated to be 48 to 52% (PH2O = 23 to 25 Torr at 37.2 degrees C). 5. The rate of inflowing air significantly (P < 0.001) affected HR, with an optimum at 3.1 LSTPD/(h.egg). 6. The age of the laying flock significantly (P < 0.001) increased water loss; this was explained by a parallel increase of the mass specific shell conductance to water vapour. 7. Finally optimum incubation conditions were deduced, giving total hatching rates of 78 to 81% of fertile eggs, improving by 5 to 8% the best results obtained routinely in commercial practice.

Animal Husbandry↗

Critical timing of sensorimotor cortex lesions for the recovery of motor skills in the developing cat.

Forelimb movements and motor skills were studied in adult cats in order to determine the effect of brain damage inflicted at different postnatal ages. The unilateral lesion included the cortical areas from which the pyramidal tract originates in cat: areas 4 and 6 corresponding to the motor cortex; areas 3, 2 and 1 corresponding to the primary somatosensory cortex; and part of area 2 prae-insularis corresponding to the secondary somatosensory cortex. Forelimb performance of a food-retrieving task requiring proximal as well as distal muscles was assessed by comparing the limb contralateral to the damaged hemisphere (affected limb) with the limb contralateral to the intact hemisphere (non-affected limb) that appeared to perform the task as well as both limbs of control animals. In simple task-related movements, all operated animals were rapidly able to achieve the goal with the affected limb, whatever the age at lesion. In complex tasks, the ability to achieve the goal with the affected limb decreased with increasing age at lesion. Recovery of distal skills, i.e. grasping and wrist rotation, did not occur in animals operated on after the 23rd postnatal day (PND), and recovery of proximal skills, i.e. amplitude and precision of the reaching movement, did not occur in animals operated on after the 45th PND. The critical time for the recovery of distal skills lies somewhere between the 23rd and 30th PND, whereas for the recovery of proximal skills it lies somewhere between the 45th and 60th PND. These critical dates for the recovery of motor skills support the Kennard doctrine. Different critical times for proximal and distal skills may be explained in terms of different stages of sensorimotor development in kitten. It is hypothesised that recovery only occurs if brain damage is inflicted before maturation of the nervous system underlying a given motor skill.

Animals↗

Recovery of distal skills after neonatal lesion of the sensorimotor cortex in the cat.

The cytoarchitectonic cortical areas containing the cells of origin of the pyramidal tract were unilaterally removed from kittens during the first postnatal month. After 5 months, the distal skills of these operated animals were analyzed using a food retrieving task. After an initial deficit, cats achieved the same performance in grasping and wrist movement with the limb contralateral to the lesion as with the opposite limb. The duration of the deficit was dependent on age at the time of lesion. Recovery of distal skills after neonatal lesion is discussed with regard to the low degree of maturity of the corticospinal tract in newborn cat.

Aging↗

[Study in the anuran amphibian Xenopus laevis, some blood characteristics and nitrogen excretion based on changes in the water osmolarity].

The pH, the osmolality and the urea and ammonia concentrations in blood, as well as the net urea and ammonia excretions, were studied in the amphibian Xenopus laevis exposed for several weeks to increased osmotic pressure (OP) of the ambient water, as a result of the addition of either NaCl or mannitol to the water. The pH and the ammonia concentration of the blood were independent of the variations of the ambient osmolarity. On the contrary, the blood osmolality and its urea concentration increased markedly when the ambient OP was augmented. The increase of ambient OP by NaCl addition to the medium augmented the urea net excretion and slightly decreased the ammonia excretion. When the increase of ambient OP resulted from the addition of mannitol in the water, excretions of urea and ammonia became negligible.

Ammonia↗

[Excretion of urea and ammonia and its effect on the acid-base balance of water in the habitat of the anuran amphibian Xenopus laevis. Action of metabolic alkalosis].

We studied in Xenopus laevis the effect of changing the salinity and the acid-base status of the ambient water on the total nitrogen catabolism and the nature of the nitrogen end products, urea and ammonia. Increase of the ambient osmolarity by addition of NaCl led to a rise in protein catabolism and to a predominant ureotelism which can approach 95% of the excreted nitrogen. The osmolarity can reach 500 mosmol. L-1 without obvious harmful effects. NaCl can then be replaced by NaHCO3 without injury to the animal as long as water alkalosis is avoided by an appropriate increase of the ambient CO2 tension, PCO2. However, if PCO2 is kept low, the resulting water metabolic alkalosis causes death within a few hours.

Acid-Base Equilibrium↗

Evaluation of transforming activity of cellular DNAs from different origins by NIH3T3 transfection test.

The NIH3T3 cell transfection test, as first described by Cooper, has been optimized, then used to examine the transforming activity of genomic DNA extracted from eucaryotic cell lines commonly used for preparing vaccines or biopharmaceuticals. Accurate assessment of technical parameters of the test has led to improvement in reproducibility, while the demonstration of dose-effect relationships has allowed the definition of applications and limits for quantitative use. We have performed the direct assessment of transforming activity of cellular DNAs from cell lines widely used in biotechnology. In particular, we have shown that genomic DNA extracted from Vero, CHO or MRC5 cells, as well as from human or murine lymphoid cells, has no detectable transforming activity on NIH3T3 cells. Lastly, it has been demonstrated that acidic pH conditions are sufficient to destroy the major part--if not all--of the transforming activity of positive control DNAs.

3T3 Cells↗

[Do the variations in water carbon dioxide pressure and PH have an effect on the nature of end products of protein catabolism, ammonia and urea, in the clawed frog Xenopus laevis?].

The effects of PCO2 and pH changes in the ambient water on the nitrogen catabolism and the proportions of the excreted nitrogenous end products, ammonia and urea, were studied in the clawed frog, Xenopus laevis, at 24 degrees C. In animals living in artificial fresh water, the exposure to a hypocapnic alkalosis (PCO2 = 0.7 Torr instead of 10 Torr) did not entail any change in the nitrogen catabolism. In animals who lived in a water loaded with NaCl and had therefore a higher oxygen consumption, an intense nitrogen catabolism and a marked ureotelism, the hypocapnic alkalosis seems to have increased the intensity of the nitrogen catabolism. In neither group were there signs of ammonia toxicity.

Ammonia↗

Molecular size characterization of bacterial capsular polysaccharide vaccines by high performance liquid chromatography.

Bacterial capsular polysaccharides are major virulence factors and some are used as vaccinal antigens. Their molecular size is an important physicochemical criterion which correlates with immunogenicity. This article describes a new application of high performance liquid chromatography (HPLC), based on molecular sieving, for such an evaluation. This HPLC method is rapid, accurate, reproducible, requires only very low amounts of product and presents good correlation with conventional gel permeation chromatography.

Bacterial Capsules↗