Biomedical subjects

L Rioux

Publications and source records attributed to L Rioux.

14 recordsLinked to original sources

PubMed2001

Challenges, status, and opportunities for studying developmental neuropathology in adult schizophrenia.

Neurodevelopmental theories of the pathoetiology of schizophrenia have been at the forefront of schizophrenia research in recent years. Support for these theories is substantial and growing. Epidemiological, phenomenological, and clinical neurobiological research have provided compelling though still circumstantial evidence. Neuropathological investigations also have provided some evidence; however, these have yet to actualize their potential for revealing the cellular and molecular nature of developmental aberrancies in this disease. This article summarizes the clinical evidence suggesting abnormal neurodevelopment in schizophrenia, outlines some of the important anatomic, cellular, and molecular mechanisms of normal central nervous system development, reviews current neuropathological findings relevant to neurodevelopment in schizophrenia, and suggests some new directions and opportunities for discovering the molecular neurodevelopmental basis of the disorder.

Atrophy↗

PubMed1998

Differential effects of protein kinase A on Ras effector pathways.

Ras mutants with the ability to interact with different effectors have played a critical role in the identification of Ras-dependent signaling pathways. We used two mutants, RasS35 and RasG37, which differ in their ability to bind Raf-1, to examine Ras-dependent signaling in thyroid epithelial cells. Wistar rat thyroid cells are dependent upon thyrotropin (TSH) for growth. Although TSH-stimulated mitogenesis requires Ras, TSH activates protein kinase A (PKA) and downregulates signaling through Raf and the mitogen-activated protein kinase (MAPK) cascade. Cells expressing RasS35, a mutant which binds Raf, or RasG37, a mutant which binds RalGDS, exhibited TSH-independent proliferation. RasS35 stimulated morphological transformation and anchorage-independent growth. RasG37 stimulated proliferation but not transformation as measured by these indices. TSH exerted markedly different effects on the Ras mutants and transiently repressed MAPK phosphorylation in RasS35-expressing cells. In contrast, TSH stimulated MAPK phosphorylation and growth in cells expressing RasG37. The Ras mutants, in turn, exerted differential effects on TSH signaling. RasS35 abolished TSH-stimulated changes in cell morphology and thyroglobulin expression, while RasG37 had no effect on these activities. Together, the data indicate that cross talk between Ras and PKA discriminates between distinct Ras effector pathways.

Animals↗

PubMed1997

Dual activity maps in primate visual cortex produced by different temporal patterns of zif268 mRNA and protein expression.

The inducible nature of the immediate-early genes (IEGs) c-fos and zif268 allows their products to be used as activity markers in the brain. The utility of such markers in general is restricted because they can resolve only neurons activated by a single stimulus. To overcome this limitation, we have developed a double-label technique that exploits the dissimilar time course of zif268 mRNA and protein induction, allowing them to be separately induced by two different stimuli and independently stained to provide a visual display of neurons that are responsive to each stimulus. Two powerful features of this new imaging technique-the possibility of staining separate populations of activated neurons and the ability to visualize them at the cellular level-should extend IEG applications in biological activity mapping.

Animals↗

PubMed1997

RalGDS functions in Ras- and cAMP-mediated growth stimulation.

Thyroid-stimulating hormone stimulates proliferation through both the cAMP-dependent protein kinase and Ras but not through Raf-1 and mitogen-activated and extracellular signal-related kinase kinase. We now report that thyroid-stimulating hormone represses mitogen-activated protein kinase activity and that microinjection of an effector domain mutant Ha-Ras protein, Ras(12V,37G), defective in Raf-1 binding and mitogen-activated protein kinase activation, stimulates DNA synthesis in quiescent and thyroid-stimulating hormone-treated thyrocytes. A yeast two-hybrid screen identified RalGDS as a Ras(12V,37G) binding protein and therefore a potential effector of Ras in these cells. Associations between Ras and RalGDS were observed in extracts prepared from thyroid cells. Microinjection of a mutant RalA(28N) protein thought to sequester RalGDS family members reduced DNA synthesis stimulated by Ras as well as cAMP-mediated DNA synthesis in two cell lines which respond to cAMP with mitogenesis. These results support the idea that RalGDS may be an effector of Ras in cAMP-mediated growth stimulation.

Cyclic AMP↗

PubMed1997

The effects of chronic levodopa treatment on pre- and postsynaptic markers of dopaminergic function in striatum of parkinsonian monkeys.

Therapeutic treatment of parkinsonian monkeys by chronic administration of levodopa (l-DOPA) leads to the development of dyskinesias and other motor fluctuations. It is unclear whether there are alterations in the dopamine system that are related to the induction of dyskinesias by l-DOPA, but recent attention has focused on the D1 receptor system. The present study assessed the consequences of chronic l-DOPA treatment in monkeys made parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on indices of the pre- and post-synaptic dopamine (DA) system. Treatment with therapeutic doses of l-DOPA led to the induction of dyskinesias in the MPTP-treated monkeys. High-pressure liquid chromatography was used for measurement of tissue levels of DA and its metabolites, and quantitative autoradiography was used to examine the regional integrity of the presynaptic DA system (by measuring [3H]mazindol binding to DA uptake sites). Quantitative autoradiography was used to measure the number of postsynaptic D1 receptors (using [3H] SCH 23390) in the striatum and pallidum of normal, MPTP alone, and MPTP monkeys treated chronically with l-DOPA. In both MPTP-treated monkeys, levels of DA and metabolites as well as [3H]mazindol binding were greatly reduced in the caudate and putamen, slightly more in dorsal than in ventral areas. However, the lack of increase in striatal DA levels along with higher [3H]mazindol binding in MPTP-plus-l-DOPA-treated monkeys suggested differences in the way DA was used after l-DOPA treatment In MPTP-treated monkeys, a significant increase (141-170% of normals) of D1 receptor numbers was observed in putamen and dorsal caudate. With l-DOPA treatment, the number of D1 receptor numbers was further elevated in caudal putamen (119-123%), dorsal caudate (110-130%), and in the internal segment of the globus pallidus (GPi; 164% of normals) of MPTP-treated monkeys as compared with MPTP treatment alone. This suggested that in MPTP-treated monkeys made dyskinetic by chronic pulsatile delivery of l-DOPA, there was enhanced production of D1 receptors in the direct striatal output to the GPi.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1996

Massive upper gastrointestinal bleeding originating from a fourth-stage duodenal diverticulum: a case report and review of the literature.

Duodenal diverticulum is well-known pathologic entity. Most such diverticula are asymptomatic and located on the second stage of the duodenum. The diagnosis is most often established by endoscopy or upper gastrointestinal radiography. Hemorrhage has been described but is an infrequent complication. We report on a patient who presented with massive upper gastrointestinal bleeding, originating from a fourth-stage duodenal diverticulum. The diagnosis was made with a combination of arteriography and scanning with technetium 99-labelled red cells. Diverticulectomy was performed with a successful outcome. This report underlines the diagnostic limits of fiberoptic endoscopy for hemorrhagic lesions located past the third stage of the duodenum.

Diverticulum↗

PubMed1993

Substance P receptors are differentially affected in Parkinson's and Alzheimer's disease.

We have quantified by receptor autoradiography the number of NK1 receptors, using [125I] Bolton-Hunter labeled substance P, in striatum and pallidum (internal (GPi) or external (GPe) segment) of patients suffering from Alzheimer's (AD) and Parkinson's disease (PD). When compared to non-neurologic controls, a significant increase in the number of NK1 sites has been observed in the striatum of PD patients. No significant differences were observed for the GPi and GPe. We observed no significant differences from controls in the number of NK1 sites in the striatum and pallidum of AD cases. However, the number of NK1 sites in the striatum of AD patients was significantly lower than that of PD patients. These results show that the expression of NK1 receptors in the basal ganglia is affected in PD.

Aged↗

PubMed1993

A fetal nigral graft prevents behavioral supersensitivity associated with repeated injections of L-dopa in 6-OHDA rats. Correlation with D1 and D2 receptors.

The effect of repeated administration of L-3,4-dihydroxyphenylalanine was studied behaviorally and biochemically in grafted versus non-grafted rats with a 6-hydroxydopamine unilateral lesion of the dopaminergic nigro-striatal pathway. Non-grafted rats receiving 14 injections of L-3,4-dihydroxyphenylalanine increased their contraversive circling while grafted rats did not, even after fourteen injections. The density of striatal dopamine receptors was examined by autoradiography using the ligands [3H]-SCH 23390 for dopamine D1 receptors and [3H]-spiperone for D2 receptors. In rats with a lesion of the nigro-striatal dopaminergic pathway, an increase of [3H]-SCH 23390 and [3H]-spiperone binding in the lesioned striatum was observed when compared with the striatum on the intact side. Chronic treatment with L-3,4-dihydroxyphenylalanine led to a further increase in D1 receptor density in the lesioned as well as the intact side. A similar pattern was observed for D2 receptors although the change did not reach significance. A graft of fetal nigral neurons brought the density of both D1 and D2 receptors on the lesioned side back to the level of the intact side. This is observed both in acutely or chronically L-3,4-dihydroxyphenylalanine treated rats. This study suggests that nigral grafts protect the striatum against L-3,4-dihydroxyphenylalanine-induced supersensitivity. It appears that the graft preserves the symmetry of the striatum even though there is an increase of D1 dopamine receptors. These results suggest that a fetal nigral graft could prevent the induction of 3-4-dihydroxyphenylalanine- induced dyskinesia in parkinsonian patients.

Animals↗

PubMed1992

Transjugular intrahepatic portacaval stent shunt as a rescue treatment for life-threatening variceal bleeding in a cirrhotic patient with severe liver failure.

Variceal bleeding in cirrhotic patients with severe liver failure that is not controllable by endoscopic sclerotherapy is a life-threatening situation. We report the case of a patient with decompensated cirrhosis (Pugh class C) who bled repeatedly from gastric varices despite multiple sessions of sclerotherapy. The portal vein was catheterized by a transjugular approach. A tract between a hepatic vein and the portal vein was created after balloon dilatation, and this opening was stented with an expandable stainless steel Palmaz stent. The portal vein pressure decreased from 35 mm Hg to 19 mm Hg after shunting. Gastric varices also were embolized. Two months later, bleeding had not recurred; the shunt remained opened and the marked decrease in portal pressure still persisted. Endoscopy showed the disappearance of gastric varices. This procedures could become a life-saving therapeutic option for such critically ill cirrhotic patients.

Catheterization↗

PubMed1991

Regional changes of striatal dopamine receptors following denervation by 6-hydroxydopamine and fetal mesencephalic grafts in the rat.

Young adult female rats received a 6-hydroxydopamine lesion in the left substantia nigra and, 3 weeks later, some of them were grafted with a cell suspension from the ventral mesencephalon of rat embryos (14-15 days old). Six months after transplantation, some grafted rats, following injection of amphetamine, had switched to turning only toward the intact side (type 1), whereas others turned toward the intact side only during the first half of the test (type 2). Levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid were, respectively, 2%, 15% and 35% of the intact side in the denervated striatum of 6-hydroxydopamine rats. Dopamine concentrations were restored to 13% and 10% of the intact side in the grafted striatum of type 1 and type 2 animals, respectively. Levels of homovanillic acid were unchanged following grafts whereas those of dihydroxyphenylacetic acid increased by 209% and 247% in the grafted striatum of type 1 and type 2 animals, respectively. The ratios of dihydroxyphenylacetic acid/dopamine as well as homovanillic acid/dopamine were low in the intact striatum whereas they increased in the denervated striatum with or without graft. The tyrosine hydroxylase immunoreactivity decreased by about 80% in the denervated striatum of 6-hydroxydopamine rats. In type 1 rats, tyrosine hydroxylase immunoreactivity revealed that the graft was localized in the dorsomedial part of the denervated striatum, whereas in type 2 animals, it was also in the medial striatum but it overlapped the dorsal and ventral parts of it equally. D1 as well as D2 dopamine receptors were measured throughout the striatum (9.0-7.6 rostral-caudal coordinates), by autoradiography, using [3H]SCH 23390 (D1 antagonist) and [3H]spiperone (D2 antagonist) binding. Supersensitive D2 receptors were normalized in the dorso- and ventromedial parts of the grafted striatum. D2 receptor density was higher in type 2 than in type 1 rats, more specifically at 8.6-8.2 rostral-caudal coordinates, where the graft was. D1 receptor supersensitivity was modest compared to D2 receptors in the striatum of 6-hydroxydopamine rats and decreased following grafts. DA receptors changes in the striatum, following fetal mesencephalic grafts, may explain the behavioral recovery seen in grafted rats.

Amphetamine↗

PubMed1991

Correlation of functional recovery after a 6-hydroxydopamine lesion with survival of grafted fetal neurons and release of dopamine in the striatum of the rat.

Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least two weeks later they were tested with amphetamine (5 mg/kg, s.c.) and apomorphine (0.25 mg/kg, s.c.). A cell suspension from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. The amphetamine test was then repeated every month for six months. The pattern of circling to amphetamine before the graft was strictly ipsiversive in all animals. From the first month we observed a progressive change and three patterns of rotation could be observed. In 21% of animals, the total number of ipsiversive turns in 90 min actually increased but during the first 20 min the animals turned contralaterally to the lesion (and to the graft). In 38% of animals, the total number of turns switched from ipsiversive to contraversive with the animals turning initially toward the intact side and during the second half of the test toward the lesion. Finally 41% of rats progressively switched to turning only toward the intact side. In all cases, maximal contraversive turning occurred during the initial 20 min. In these rats, tyrosine hydroxylase-positive cells were detected mainly in the dorsal striatum with a few in the central portion. Moreover there was a strong correlation between the number of surviving grafted neurons and the growth of their fiber into the host striatum and the extent of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

PubMed1991

Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants.

The effect of fetal mesencephalic transplants on dopamine receptor supersensitivity has been studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least one month later they were tested with apomorphine (0.25 mg/kg, s.c.), amphetamine (5 mg/kg, s.c.), LY 171555 (D2 agonist) (0.5 mg/kg, i.p.) and CY 208243 (D1 agonist) (0.5 mg/kg, s.c.). A suspension containing approximately 1.5 x 10(6) cells from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. Six months later, grafted dopamine neurons reinnervated the medial part of the dorsal striatum, increased the dopamine level and reversed the rotational asymmetry evoked by amphetamine. Apomorphine given four months post-transplant still elicited contraversive circling but the number of turns was reduced. Circling evoked six months post-transplant by CY 208243 or LY 171555 was significantly less in grafted rats than in lesioned non-grafted rats. The density of dopaminergic receptors in the striatum of grafted and lesioned rats was examined by autoradiography by means of in vitro binding with [3H]SCH 23390 for D1 receptors and [3H] spiperone for D2 receptors. The results show that intrastriatal nigral transplants decrease the supersensitivity of the D2 receptors and to a lesser extent of the D1 receptors. Normalization of D2 receptors may explain the decrease of behavioral supersensitivity following administration of apomorphine and D2 agonist in grafted rats. D1 receptors were less affected by the lesion and also less normalized than D2 receptors by the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Fetal dopamine neuron transplants prevent behavioral supersensitivity induced by repeated administration of L-dopa in the rat.

We have studied in adult rats bearing a unilateral nigral lesion the effect of nigral grafts into the striatum on behavioral supersensitivity induced by chronic treatment of L-DOPA (100 mg/kg i.p.) plus benserazide (50 mg/kg i.p.). Repeated administration of L-DOPA increases contraversive circling. In rats without graft the contraversive circling was significantly increased after 8 and 14 daily injections of L-DOPA. On the other hand, the animals with transplants showed no such increase. Behavioral supersensitivity induced by repeated treatment of L-DOPA is often correlated with dyskinesia observed in the Parkinsonian patients. This suggests that the graft might be able to prevent this secondary effect.

Animals↗

PubMedDate not supplied

Actin paracrystalline sheets formed at the surface of positively charged liposomes.

Paracrystalline aggregates of F-actin spontaneously assemble at the surface of positively charged liposomes. This single-layered paracrystalline array is made up of parallel and juxtaposed actin filaments aligned in register and showing the typical 36-nm periodicity which corresponds to the half-pitch of the double helix strand. This crystallization of pure actin results from a direct interaction between actin and positively charged lipids and does not occur with negative or neutral lipids.

Actins↗