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Biomedical subjects

G Geraud

Publications and source records attributed to G Geraud.

At least 19 recordsLinked to original sources

N-cadherin and N-CAM in myoblast fusion: compared localisation and effect of blockade by peptides and antibodies.

The expression and distribution of two cell adhesion molecules, N-cadherin and N-CAM, at the surface of cultured leg muscle cells from 11-day-old chicken embryos were studied and compared. N-cadherin, which was expressed by fusing myoblasts, was down-regulated on old myotubes while N-CAM was still present. Both molecules, as viewed by confocal microscopy, appeared to have coaccumulated at the areas of contact between fusing myoblasts. However, immunogold electron microscopy did not reveal significant colocalization of N-cadherin and N-CAM, and their segregation after antibody-induced patching suggested the absence of direct interactions between N-cadherin and N-CAM. The role of the Ca2+ dependent cell adhesion molecule N-cadherin in myogenesis was investigated. Myoblast fusion was inhibited (1) with a synthetic peptide containing the H-A-V sequence and (2) with a monoclonal anti-N-cadherin antibody, demonstrating that N-cadherin-mediated cell adhesion is required for myoblast fusion. Under the same conditions no effect of anti-N-CAM antibodies was observed. Taken together these observations suggest that N-cadherin, acting independently from N-CAM, is a major cell adhesion molecule involved in embryonic myoblast fusion in vitro.

Amino Acid Sequence

Computer reconstruction of nucleolar architecture by interactive three-dimensional color display.

The first complete three dimensional ultrastructural reconstruction of pancreatic cell nucleoli, was done using EM and computer 3D-assisted reconstruction of serial sections with interactive 3D back-to-front and color display methods based on voxel representation. The purpose of the study was to depict the architecture of the nucleolar components. We obtained information about the location of the nucleolus within the nuclear volume and about the shape and polarity of the 3 main nucleolar territories.

Animals

Dipeptidyl peptidase IV expression in rat jejunal crypt-villus axis is controlled at mRNA level.

The expression of dipeptidyl peptidase IV (DPP IV), an intestinal brush-border hydrolase, has been studied in the rat jejunum crypt-villus axis. DPP IV enzyme activity is lower in crypt cells than in villus cells. Indirect immunofluorescence studies, using a polyclonal antibody raised against purified DPP IV, show a gradient of immunoreactivity from the crypts to the villi that was quantified using confocal laser scanning microscopy. Accordingly, Western blot analysis demonstrates that the steady-state amount of DPP IV is much lower in crypt cells than in villus cells. Northern blot analysis was performed using our cDNA probe for human DPP IV that presents more than 94% homology with rat DPP IV cDNA. Results clearly show that there is approximately seven times less DPP IV mRNA in crypt cells than in villus cells. We conclude that the differentiation-dependent expression of DPP IV in rat jejunum is primarily controlled at the mRNA level.

Animals

Behaviour of nucleolar proteins in nuclei lacking ribosomal genes. A study by confocal laser scanning microscopy.

The behaviour of nucleolar proteins in cycling PtK1 cells and in micronuclei with or without NORs was investigated by immunofluorescence using antibodies from autoimmune sera and confocal laser scanning microscopy. These antibodies were shown by electron microscopy to recognize antigens confined to only one of the three basic nucleolar components: fibrillar centres (FC), dense fibrillar component (DFC) and granular component (GC). Serial optical sections allowed us to determine the three-dimensional organization of these components in the nucleolus of cycling cells. Furthermore, clear differences were found in the distribution of the various antigens in micronucleated cells. Three patterns could be observed: (1) the FC antigens were found mainly in the nucleoli, but also in varying amounts in the dots; (2) surprisingly, the DFC antigens were found to accumulate preferentially in the dots; (3) the GC-specific marker stained intensively the nucleoli as well the dots. The results are interpreted with regard to possible mechanisms for targeting nucleolar proteins to the site of nucleolar formation.

Biomarkers

Superoxide dismutase (SOD) and the PAF-antagonist (BN 52021) reduce small intestinal damage induced by ischemia-reperfusion.

Oxygenated free-radicals appear to play a prominent role in mediating damage associated with gastrointestinal diseases. Production of reactive oxygen metabolites in ischemia-reperfusion involves oxidases found in resident phagocytic cells and microvascular and mucosal epithelial cells. Platelet activating factor (PAF), a phospholipid associated with inflammatory disorders, has been shown to both prime and amplify the release of superoxide anion and hydrogen peroxide from polymorphonuclear neutrophils and macrophages stimulated by FMLP or PMA. To further elucidate the involvement of free radicals in intestinal damage and the potential role of PAF in their production, we examined the effect of superoxide dismutase (SOD) and BN 52021 (ginkgolide B) on ischemia-reperfusion induced damage in the small intestine. The study involved 32 Sprague-Dawley rats (100-200 g) divided into four groups. Three of these groups were subjected to occlusion of the mesenteric artery 30 mins followed by 24 h reperfusion. On 2 groups SOD (15,000 U/kg/iv) and BN 52021 (20 mg/kg/po) were administered 45 mins before arterial occlusion. Following the 24 h reperfusion, the rats were sacrificed after overnight fasting. The jejunum and ileon were removed and fixed for morphological examination. Lesions in the small intestine were quantified. The results showed extensive necrosis, hemorrhage, oedema and neutrophil invasion in the jejunal and ileal mucosa. This injury was significantly reduced by SOD (15,000 U/kg/iv) and BN 52021 (20 mg/kg/po) pretreatment. In conclusion, free-oxygenated radicals appear to mediate reperfusion damage in the small intestine and PAF appears to be involved in the genesis of these toxic products. Thus, SOD and BN 52021 may be considered as protectors against ischemic disorders.

Animals

A 116,000 Mr nucleolar antigen specific for the dense fibrillar component of the nucleoli.

In ATT, a human autoimmune serum, we found anti-nucleolar antibodies that recognized nucleolar antigens confined to a single nucleolar compartment, the dense fibrillar component (DFC). We localized these antigens by immunoelectron microscopy in DFC of HeLa cell nucleoli both on Lowicryl sections and cryoultrathin sections without embedding. The antigens were solubilized by incubation with 2M NaCl but not by RNase or DNase treatment. The ATT serum crossreacted with rat liver nucleoli and PtK1 cell nucleoli in which immunofluorescence labelling displayed a clumpy pattern. During mitosis, the antigens dispersed in the cytoplasm until late telophase, when they gathered in the prenucleolar bodies. In human peripheral lymphocytes, or HeLa cells treated with actinomycin D, the antigens were still present but the fluorescence intensity decreased. By immunoblotting using human nuclear extracts, the ATT serum bound to a 116,000 Mr protein at dilutions up to 1:2000. The reactivity of this band diminished with actinomycin D-treated nuclear extracts. Two minor bands were also observed at 97 and 70K (K = 10(3) Mr). Immunopurification by competition or elution demonstrated that the 116K antigens were at the origin of the nucleolar labelling. This DFC marker appeared to be different from the NOR-silver-stained proteins, which in our preparations exhibited apparent molecular weights of 105, 80 and 38-40K. In addition, these 116K antigens did not exhibit the characteristics described for DNA topoisomerase I, fibrillarin or nucleolin. We propose the 116K antigen as a new marker of the DFC of the nucleoli.

Aged

Propranolol does not alter cerebral blood flow and functions in cirrhotic patients without previous hepatic encephalopathy.

Since it has been suggested that propranolol could lead to hepatic encephalopathy, we undertook a study to assess the effects of propranolol on cerebral blood flow and cerebral functions. Sixteen patients with alcoholic cirrhosis and large esophageal varices and without major hepatic dysfunction (Child-Pugh score less than 14) or previous hepatic encephalopathy were randomized to receive either propranolol or placebo. The following measurements were performed before and 15 min after single intravenous administration of 15 mg propranolol or placebo and again 1 week after chronic oral administration of propranolol 160 mg per day or placebo: cerebral blood flow by the xenon-133 inhalation technique, quantitative electroencephalogram, psychometric test (number connection test), arterial ammonia, pH and pCO2, resting and exercise heart rates (after single administration, electroencephalogram, number connection test and biochemical measurements were not performed). Cerebral blood flow was not significantly modified by treatment (propranolol group: 80 +/- 23 vs. 76 +/- 11 and 83 +/- 9; placebo group: 73 +/- 10 vs. 75 +/- 11 and 81 +/- 18 ml per 100 gm per min, respectively, before and after single and repeated administration). Likewise, neither of the two treatments significantly altered number connection test, quantitative electroencephalogram index, arterial ammonia, pH and pCO2. We conclude that, in this population of cirrhotic patients, propranolol did not alter cerebral blood flow or neuropsychological functions. As a consequence, hemodynamic alterations cannot be considered as causes of possible cerebral side effects of propranolol in cirrhotic patients without severe hepatic dysfunction and previous hepatic encephalopathy.

Ammonia

[Cerebral gliomatosis. An anatomoclinical case].

Gliomatosis cerebri is a glial neoplastic process. It is diffusely distributed through brain structures whose anatomical configuration remains intact. Clinical diagnosis of this rare disease is difficult. The symptoms are varied and biological and radiological data are not specific. The case reported shows the characteristic features of the disease. Diagnosis was possible only on autopsy, in spite of several previous clinical and biological investigations and nuclear magnetic resonance study.

Adult

Three-dimensional computer reconstructions from serial sections of cell nuclei.

The analysis of ultrathin serial sections as 3-dimensional (3D) information requires interpretation and display of a large amount of data. We suggest a simple way to solve this problem; it permits presentation of a series of sections as a 3D color image of good quality. It involves a picture system with specialized hardware and software written for this purpose. 3D images of cellular organelles have been drawn either by manually defining the contour of the objects or by thresholding of the volumes in the structures. These 2 methods allow rapid drawing of the image on the screen. It is possible to determine the position, shape and size of 3D structures. This interactive system allows the user to choose between several options: colors, removal of parts of the object, and cutout.

Animals

Reversibility of hemodynamic hypofrontality in schizophrenia.

Regional cerebral blood flow (CBF) was studied in 51 young schizophrenics. A significant decrease of CBF was seen in frontal and prefrontal regions (hypofrontal pattern) in chronic patients whose disease had evolved for more than 2 years and who were in remission. This hypofrontal pattern was reversible, as it disappeared during exacerbation of the disease. In 10 patients who had not been treated with neuroleptics for several weeks, we found a dopaminergic hypersensitivity in the frontal lobes, as a weak dose of piribedil restored near-normal frontality. This may reflect either the role of neuroleptic washout or a primitive dopaminergic depletion, as proposed by some authors in the chronic form of schizophrenia.

Adult

[Migraine and the idiopathic Raynaud phenomenon].

The successive onset of spasms of distal arteries of the limbs and complicated migraine in a young migrainous woman raised the possibility of a common mechanism for both disorders. Three similar cases have been reported and two recent epidemiological studies have shown the frequent association of migraine attacks and Raynaud's phenomenon or variant angina in a individual patient. The possible role of vasospasm in triggering the migrainous aura is discussed.

Adult

Hemodynamic and metabolic factors in human cerebral ischemia.

Hemodynamic and metabolic cerebral measurements (CBF, CMRO2, CMRG, CSF) were evaluated in stroke patients. To investigate the effects of chronic cerebral circulatory insufficiency, CBF and CMRO2 were also studied. Further nontraumatic investigations of CBF measurement will allow a better understanding of clinical cases.

Acidosis