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Biomedical subjects

J Pradel

Publications and source records attributed to J Pradel.

At least 19 recordsLinked to original sources

Homeotic control in Drosophila; the scabrous gene is an in vivo target of Ultrabithorax proteins.

The regulatory functions of transcription factors encoded by the Ultrabithorax (Ubx) gene initiate genetic programmes essential for segmental identity and morphogenesis in Drosophila. Based on the formation of DNA-protein adducts in intact nuclei and immunoselection procedure, we cloned genomic targets for Ubx proteins. One clone was studied in detail. It encompasses parts of the last intron and exon of the scabrous (sca) gene, which encodes a secreted protein involved in cellular communication during neurogenesis. Five motifs, presenting the ATTA core, which is shared by most homeodomain binding sites, were found in the nucleotide sequence of this clone. We detail here the dynamic pattern of sca transcript accumulation during embryogenesis and show that mutation of Ubx results in the ectopic transcription of sca in the first abdominal segment. We propose that a direct interaction of Ubx with cis-acting elements in sca negatively regulates the gene. Transcript localization in several combinations of deficiencies in the Bithorax complex (BX-C) indicates that sca is downregulated by abdominal A (abdA) and Abdominal B (AbdB), and suggests that it is a common target of the three genes of BX-C.

Animals

Cell lineage-specific expression of modulo, a dose-dependent modifier of variegation in Drosophila.

Variegation in Drosophila is a manifest illustration of the important role played by chromatin structure in gene expression. We have isolated mutants of modulo (mod) and shown that this gene is a dominant suppressor of variegation. Null mutants are recessive lethal with a melanotic tumour phenotype. The mod protein directly binds DNA, which indicates that it may serve to anchor multimeric complexes promoting chromatin compaction and silencing. Using a specific monoclonal antibody we examined by immunocytochemistry the accumulation pattern of mod protein during embryogenesis. The protein is first detected before the blastoderm cellularization in all somatic nuclei, precisely when pericentromeric heterochromatin becomes visible. After the first cell division, mod protein is expressed in lineages of specific embryonic primordia. Based on its dominant phenotype, expression pattern and DNA-binding activity of its product, we propose that mod regulates chromatin structure and activity in specific cell lineages.

Animals

Acute abdomen of unknown origin: impact of CT on diagnosis and management.

A prospective study was performed including 40 patients with an acute abdominal syndrome presenting difficulties in defining the etiology. All patients underwent an emergency computed tomographic (CT) scan. The CT scan made the syndrome's diagnosis in 95% of cases and it permitted the detection of a lesion in 57.5% of cases. The diagnostic impact of CT scan was significant (p less than 0.01). The value and the specific contribution of CT in various diseases were analyzed. CT allowed appropriate therapeutic decisions in 95% of cases where clinical examination performance was positive in only 60% of cases. We had two negative CT results leading to an inappropriate therapeutic decision; it consisted of two cases of undiagnosed appendicitis. CT modified the primary therapeutic strategy in 30% of cases and avoided seven laparotomies.

Abdomen, Acute

[The posterior interparietoperitoneal spaces or retroperitoneal spaces. 1: Normal topographic anatomy].

The posterior spaces between the wall and peritoneum or extraperitoneal spaces are located between the visceral retrocolic and retro-duodenopancreatic fascias anteriorly and the parietalis fascia posteriorly. They were studied using an anatomic and computed tomographic comparison. The propria fascia (lateroconal fascia) divided into the anterior and posterior layers of the perirenal fascia. The fascias delimitate two anterior and posterior pararenal spaces around the kidney compartment and two anterior and posterior perirenal spaces in the compartment itself. These spaces extended above and below the renal compartment from the diaphragm to the pelvis. These large spaces composed of fat and organs can assume the guided migration of pathologic processes or their spread according to the importance of the fascias barriers. They below to the genito-urinary region. The extraperitoneal spaces are related anteriorly to the retroperitoneal alimentary organs: duodenum, pancreas, ascending and descending colon depending of the alimentary region. They are related posteriorly with the abdominal wall and its own fat. The individuality and the interdependance of these three territories (alimentary, genito-urinary and abdominal wall) and their consequences for pathologic CT scan imaging will be discussed in the second part of this paper.

Humans

[The posterior interparieto-peritoneal or retroperitoneal spaces. 2: Pathological x-ray computed tomographic image].

The old reports about the interparieto-peritoneal spaces described particularly the renal space and its environment. The CT scan has modified the in vivo study of the extraperitoneal spaces (E.P.S.) and brought the question of the acquired knowledge up again. An anatomical research was performed in the first part of this study which describes the structures limited between the parietalis fascia and visceral peritoneal fascias. These are the true EPS which the main element is the propria fascia of Sappey (lateroconal fascia) and its anterior and posterior renal double layers. All these lamellar structures limits spaces variably infiltrated with fat tissue: the anterior pararenal space almost virtual, the posterior pararenal space which continues till the Bogros space and the anterior and posterior renal spaces of the renal compartment which the fat continues till the bladder and accompanies the ureter. The second part of this study precises some notions of general topography which are necessary for reading abnormal CT scan images. This part reminds the aortic and arterial general organization of the vertebrates as described by Mackay. It underlines the architectural importance of the three areas so defined: parietal or peripheral, intermediate or mesoblastic genitourinary and deep lateral or digestive endoblastic. These three areas corresponds to the three vascular aortic circles. It emphasized the importance to accept in practice the notion of visceral joining fascia which has been proved in adult people. The longitudinal architecture of the compartments is precise with respect to their appartenance to one among the three arterial arches of Mackay. What the anatomy suggest, the pathology can prove. Several pathological processes are studied on CT scan: large hemorrhagic or necrotic collections in acute pancreatitis, abnormalities or diseases of renal or adrenal compartments, extraperitoneal mesenchymomas, diseases of the psoas compartment. All these observations are analysed in order to explain anatomical and CT scan findings. This study refers not only to the oldest researches which are still valuable but also to the most recent controversies. All the questions are not solved using the clearest schemes.

Abdomen

[Role of imaging in the exploration of the adrenal glands].

Currently, the major method of adrenal gland imaging is computed tomography. This method allows demonstration of normal adrenals and the diagnosis of adrenal masses (if these are greater than 1 cm in diameter). The examination should be directed by clinical signs and known laboratory investigations. Computed tomography is therefore the first line investigation to perform. Certain lesions may be better demonstrated by other methods: MRI and MIBG scintigraphy offer a greater specificity in the investigation of pheochromocytomas. In addition, scintigraphy can identify possible ectopic tumours or recurrences. Selective catheterisation of the adrenal veins allows aldosterone and cortisone secretions to be assayed. There remains the problem of the incidental finding of adrenal masses in either an asymptomatic patient or in the context of investigation of spread of a know cancer. These lesions may benefit from diagnostic percutaneous guided biopsy.

Adrenal Gland Neoplasms

Modulo, a new maternally expressed Drosophila gene encodes a DNA-binding protein with distinct acidic and basic regions.

We have cloned, following an immunological screen of an expression library, five cDNA clones encoding the modulo antigen, a DNA-binding protein differentially expressed during Drosophila development. In addition a series of overlapping cDNA and genomic clones were also isolated. This protein is the product of a 2.2 kb mRNA that is encoded by a single genetic locus (100F). Analysis of the complete 544 amino-acid sequence, deduced from nucleotide sequence of cDNAs, shows that the polypeptide exhibits a primary structure with distinct charged regions, a modular structure found in several eukaryotic nuclear proteins, either transcription regulators or structural factors. The amino and carboxyl termini are rich in basic residues. The first third of the sequence contains a long domain comprised almost entirely of glutamic and aspartic acid residues. A typical cAMP dependent phosphorylation site and five potential glycosylation sites have been detected in the amino-acid sequence. Computer searches fail to reveal any significant homology with known proteins. Developmental pattern of transcription of the modulo gene indicates that messengers are maternally provided to the embryos and that zygotic transcription is required during subsequent development.

Amino Acid Sequence

Expression of laminin and of a laminin-related antigen during early development of Drosophila melanogaster.

This paper reports the characterization of two immunologically related proteins that may be involved in cell adhesion during Drosophila development. These proteins, laminin chain A and a 240K component, share the epitope recognized by monoclonal antibody RD3 (Mab RD3). The two antigens show different developmental expression profiles. Laminin is detected only from 6 to 8 h of development onwards; its concentration increases during embryogenesis to reach steady-state value in larvae, pupae and adult flies. By contrast, the 240K antigen, not found in oocytes, is present before blastoderm stages; its concentration increases during gastrulation, decreases at the end of organogenesis and the antigen is no longer detected in third instar larvae. Light and electron microscope immunolocalization in imaginal discs indicates that laminin is distributed apically in the lumen and basally in the basal membrane that surrounds the nonevaginated disc. During morphogenesis laminin is detected at the basal side of the evaginating part of the disc epithelium. Immunolocalization on paraffin sections of early embryos suggests that the 240K antigen is related to (1) cell formation and polarization in association with cytoskeleton components, (2) establishment of cell-extracellular substratum interactions during the blastoderm cell sheet organization and (3) basement membrane deposition during embryonic germ cell layer segregation. This 240K protein is poorly or not glycosylated, is resistant to chondroitinase ABC and collagenase and appears therefore as a new extracellular component that might be specifically involved in early processes of morphogenesis.

Animals

Nuclear antigens differentially expressed during early development of Drosophila melanogaster.

To obtain specific immunological probes for studying molecular events involved in gene activation during early development of Drosophila, we have produced monoclonal antibodies directed against nuclear proteins differentially expressed in time and space during embryogenesis. Twenty-five antibodies against nuclear antigens detected after the onset of zygotic genome transcription were obtained. These antigens have been distributed into six categories depending on their reactivity in dot-blot, in Western-blot and in immunofluorescence on embryo frozen section assays. Six antigens (fifth and sixth categories) are stage-, but not tissue-specific and are present in all nuclei of the embryo after the blastoderm stage. Ten antigens, the third and fourth categories, did not react on immunofluorescence and have not been characterized for a possible tissue specificity. Antigens of the first and second categories are stage- and tissue- specific. Two of them are of particular interest. The first (250 kd, recognized by the monoclonal antibody GB7) is preferentially expressed in nuclei of the ventral nerve cord, whereas the other (65 kd, recognized by the monoclonal antibody LA9) is located in nuclei of the gut and associated structures.

Animals

Cystic renal cancers: CT characteristics.

The preoperative distinction between renal cyst and tumor has long been a dilemma. A cystic renal adenocarcinoma may appear similar to a largely necrotic tumor or a cancer incorporated into a cyst or arising from a cyst wall. Overall, these cystic cancers present the same preoperative features. In our series of 15 cases, the characteristic pattern on computed tomography scans included size greater than or equal to 10 cm, localized thickening of cyst walls with contrast enhancement, and irregularly and poorly defined implantation in the kidney.

Adenocarcinoma

Local recurrence after nephrectomy for primary renal cancer: computerized tomography recognition.

We diagnosed by computerized tomography 15 local recurrences in 88 patients who had undergone nephrectomy for renal cancer, with no false positives and 1 false negative. This over-all low rate (17 per cent) probably is owing to the fact that computerized tomography scans were done in patients in good clinical condition. Local recurrence was noted in 3 of 59 asymptomatic patients and in 12 of 19 patients with local symptoms. No recurrence was noted in 10 patients with general symptoms. Thus, 20 per cent of local recurrences were asymptomatic and 80 per cent presented with local symptoms. High local recurrence rates were found in cases of transitional cell carcinoma with whole wall involvement or extension to adjacent tissues (4 of 8 patients, 50 per cent), clear cell adenocarcinoma with lymph node involvement (3 of 7 patients, 43 per cent) and partial nephrectomy (3 of 6 patients, 50 per cent). Therefore, we consider such patients to be at high risk. Our study demonstrates that computerized tomography enables earlier, accurate diagnosis of smaller local recurrence in asymptomatic patients and provides a sensitive, reliable, noninvasive, repetitive method of evaluation of clinical treatment trials. Routine followup should be reserved for high risk patients.

Adenocarcinoma

On the activation of fructose-1,6-bisphosphatase of spinach chloroplasts and the regulation of the Calvin cycle.

Activation by light of spinach fructose-1,6-bisphosphatase is mimicked by dithiothreitol. This process of activation by dithiothreitol implies the specific reduction of two disulfide bridges and a conformation change of the enzyme that makes eight sulfhydryl groups available. The activated enzyme has an apparent allosteric kinetic behavior with respect to both fructose 1,6-bisphosphate and magnesium.

Binding Sites

Substrate-binding isotherms of spinach chloroplastic fructose-1,6-bisphosphatase and the photoregulation of the Calvin cycle.

Fluorescence titration experiments of chloroplastic fructose-1,6-bisphosphatase by fructose bisphosphate and magnesium have been effected using the inactive dimeric, the inactive tetrameric and the active tetrameric enzyme forms. Magnesium binding to the inactive dimeric enzyme exhibits a positive cooperativity whereas fructose 1,6-bisphosphate exhibits no cooperativity at all. The binding of either magnesium or fructose bisphosphate to the inactive oxidized tetramer exhibits a succession of negative and positive cooperativities (mixed cooperativity). Upon reduction of the inactive tetramer by dithiothreitol and activation, the ligand binding properties of the enzyme are changed. Magnesium and fructose bisphosphate are bound to the active enzyme with a positive cooperativity. Non-linear least-square fitting allows one to estimate thea binding constants, and therefore the free energy of binding of either magnesium or fructose bisphosphate to the various forms of the enzyme. Whatever the state of fructose-1,6-bisphosphatase, one ligand is bound per subunit. The affinity constants of magnesium for the active or inactive enzyme forms are much greater than those of fructose bisphosphate. This suggests that the metal ion gives to the enzyme the right conformation to bind the sugar phosphate.

Binding Sites

Visibility and thickening of the renal fascia on computed tomograms.

The renal fascia can be seen on CT scans (using appropriate window settings) in most patients except those with very little fat. CT confirms current anatomical concepts; however, contrary to the illustrations shown in the literature, it clearly demonstrates that the anterior pararenal space normally exists only at the level of the retroperitoneal organs. A lesion would distend the space. While visualization of the renal fascia on normal urograms may be an indication of renal disease, a thin renal fascia on CT scans has no pathological significance. Thickening is nonspecific: it is not pathognomonic of tumor, nor is it helpful in differentiating pancreatitis from neoplasm. On the other hand, lack of fascial thickening may be helpful in ruling out renal extension of a neighboring lesion.

Carcinoma, Hepatocellular

[Angiographic exploration of a case of a case of adrenal APUD adenoma secreting three hormones: VIP, catecholamines, and somatostatin (author's transl)].

An APUD adenoma of the right adrenal was discovered in an adult after angiography and compted tomography The tumor had provoked a WDHH syndrome. Selective venous sampling before operation demostrated the presence in the tumor of hormonal secretions (VIP and catecholamines). The patient recovered after excision of the tumor, which contained large quantities of intracellular somatostatin and VIP.

Achlorhydria