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O Roche

Publications and source records attributed to O Roche.

33 records · Page 2Linked to original sources
PubMed2001

Ligand-protein database: linking protein-ligand complex structures to binding data.

In computational structure-based drug design, the scoring functions are the cornerstones to the success of design/discovery. Many approaches have been explored to improve their reliability and accuracy, leading to three families of scoring functions: force-field-based, knowledge-based, and empirical. The last family is the most widely used in association with docking algorithms because of its speed, even though such empirical scoring functions produce far too many false positives to be fully reliable. In this work, we describe a World Wide Web accessible database that gathers the structural information from known complexes of the PDB with experimental binding data. This database, the Ligand-Protein DataBase (LPDB), is designed to allow the selection of complexes based on various properties of receptors and ligands for the design and parametrization of new scoring functions or to assess and improve existing ones. Moreover, for each complex, a continuum of ligand positions ranging from the crystallographic position to points on the surface of the protein receptor allows an assessment of the energetic behavior of particular scoring functions.

Databases, Factual↗
PubMed2001

Identification of novel VMD2 gene mutations in patients with best vitelliform macular dystrophy.

ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8. Direct sequencing indicated that these shifts are caused by mono-allelic transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel "silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and 1712T>C. Hum Mutat 17:235, 2001.

Base Sequence↗
PubMed2001

[Characteristics of retinal detachment in children].

INTRODUCTION: Pediatric retinal detachments differ from adult retinal detachments in their etiologies, prognosis and treatment. The aims of this study were the analysis and long-term follow-up of a group of pediatric retinal detachment patients. PATIENTS AND METHODS: All the cases of juvenile retinal detachments treated in our department between 1987 and 1999 were retrospectively studied. The age at the time of diagnosis, etiology, initial topography of the detachment, treatments undertaken, follow-up, and final results were recorded. RESULTS: The study investigated 64 eyes of 53 children. The follow-up was longer than 6 months for 31 eyes, with a mean follow-up of 39.5 months. The main etiologies were traumatism, high myopia, and affections leading to an exudative retinal detachment such as retinoblastoma and Coats disease. Circular scleral buckling was often used because of the vitreous cohesiveness in children. A vitrectomy was frequently associated to treat severe proliferative vitreoretinopathy. The final visual acuity was higher than 0.05 in 32% of the cases. DISCUSSION: The etiological features, late diagnosis and frequency of proliferative vitreoretinopathy are responsible for the greater severity of retinal detachments in children. These factors associated with amblyopia lead to poor visual prognosis. CONCLUSION: Retinal detachment in children remains a severe pathology. However the prognosis seems to be improving with progress in examination techniques and surgery methods.

Adolescent↗
PubMed2000

Characterization of two members of the maize gene family, Incw3 and Incw4, encoding cell-wall invertases.

Two maize putative cell-wall invertase genes (Incw3 and Incw4) have been isolated by screening a genomic DNA library (Zea mays L. W22) using the cDNA probes encoding the two maize cell-wall invertases Incw1 and Incw2. The Incw3 and Incw4 genes contain six exons/five introns and five exons/four introns, respectively. The protein sequences deduced from both genes revealed a beta-fructosidase motif and a cysteine catalytic site known to be conserved in invertase genes. A detailed analysis of the protein and nucleotide sequences provides evidence that the Incw3 and the Incw4 genes encode putative cell-wall invertases. Furthermore, the isoelectric point deduced from the INCW4 protein sequence suggested that the Incw4 gene may encode a unique type of cell-wall invertase unbound in the apoplast. Gene expression studies using RT-PCR and in-situ RT-PCR hybridization showed that the Incw3 expression is organ/tissue-specific and developmentally regulated. In contrast, the Incw4 gene is constitutively expressed in all vegetative and reproductive tissues tested.

Amino Acid Sequence↗
PubMed1999

Theoretical study of the conformation of the H-protein lipoamide arm as a function of its terminal group.

The glycine decarboxylase complex consists of four different proteins (the L-, P-, H-, and T-proteins). The H-protein plays a central role in communication among the other enzymes, as its lipoamide arm interacts successively with each of the components of the complex. The crystal structures of two states of the H-protein have been resolved: the oxidized form, Hox at 2 A and the methylamine-loaded form, Hmet at 2.2 A. However, the position of the arm for the reduced form, Hred, is still unknown. We have performed numerical free-energy calculations in order to better understand the differences in the structures and to elucidate the conformation of the arm in Hred. The results of the simulations are in agreement with the crystallographic results, as the minima of the free energy surface for Hox and Hmet correspond to the crystal structures. For Hred, we observe a single minimum in which the arm is on the surface of the H-protein, close to its position in the Hox structure. In all of our simulations, the lower, lysine portion of the arm remains bound to the protein, which substantially reduces the number of accessible arm configurations. An analysis of the stability of Hmet in the cavity shows that electrostatic interactions are crucial for locking the arm in the bottom of the cavity, especially near Glu14. In addition, the analysis shows that there is a water molecule, also observed in the crystallographic structure, that binds to the arm's terminal NH3+ group and helps to fix it in the cavity. In conclusion, because of the close agreement of the results of our calculations with the available experimental evidence, we are able to suggest a structural basis for the observed behavior. Proteins 1999;36: 228-237.

Amino Acid Oxidoreductases↗
PubMed1999

Simulations of the T <--> R conformational transition in aspartate transcarbamylase.

Aspartate transcarbamylase (ATCase) from Escherichia coli is one of the best known allosteric enzymes. In spite of numerous experiments performed by biochemists, no consensus model for the cooperative transition between the tensed (T) and the relaxed (R) forms exists. It is hypothesized, however, that changes in the quaternary structure play a key role in the allosteric properties of oligomeric proteins such as ATCase. Previous normal mode calculations of the two states of ATCase illustrated the type of motions that could be important in initiating the transition. In this work four pathways for the transition were calculated using the targeted molecular dynamics (TMD) method without constraint on the symmetry of the system. The most important quaternary structure changes are the relative rotation and translation of the catalytic trimers and the rotations of the regulatory dimers. The simulations show that these quaternary changes start immediately and finish when about 70% of the transition is completed whereas there are tertiary changes throughout the transition. In agreement with the work of Lipscomb et al., it was found that the relative translation between the catalytic trimers appears to play a central role in allowing the transition to occur. In all the simulations differences are observed in the opening and closing behaviours of the domains in the catalytic and regulatory chains that could provide a structural interpretation for the results of certain site-directed mutagenesis experiments. Overall the motions of the subunits are concerted even though the constraint imposed on the TMD method does not explicitly require that this be so.

Aspartate Carbamoyltransferase↗
PubMed1998

Mitochondrial localization of a NADP-dependent [corrected] isocitrate dehydrogenase isoenzyme by using the green fluorescent protein as a marker.

In this work, we describe the isolation of a new cDNA encoding an NADP-dependent isocitrate dehydrogenase (ICDH). The nucleotide sequence in its 5' region gives a deduced amino acid sequence indicative of a targeting peptide. However, even if this cDNA clearly encodes a noncytosolic ICDH, it is not possible to say from the targeting peptide sequence to which subcellular compartment the protein is addressed. To respond to this question, we have transformed tobacco plants with a construct containing the entire targeting signal-encoding sequence in front of a modified green fluorescent protein (GFP) gene. This construct was placed under the control of the cauliflower mosaic virus 35S promoter, and transgenic tobacco plants were regenerated. At the same time, and as a control, we also have transformed tobacco plants with the same construct but lacking the nucleotide sequence corresponding to the ICDH-targeting peptide, in which the GFP is retained in the cytoplasm. By optical and confocal microscopy of leaf epiderm and Western blot analyses, we show that the putative-targeting sequence encoded by the cDNA addresses the GFP exclusively into the mitochondria of plant cells. Therefore, we conclude that this cDNA encodes a mitochondrial ICDH.

Amino Acid Sequence↗
PubMed1998

Mapping of a congenital microcoria locus to 13q31-q32.

Congenital microcoria is an autosomal dominant disorder characterized by a pupil with a diameter <2 mm. It is thought to be due to a maldevelopment of the dilator pupillae muscle of the iris, and it is associated with juvenile-onset glaucoma. A total genome search for the location of the congenital microcoria gene was launched in a single large family. We found linkage between the disease and markers located on 13q31-q32 (Zmax = 9.79; theta = 0). Haplotype analysis narrowed the linked region to an interval <8 cM between markers D13S1239 proximally and D13S1280 distally.

Chromosome Mapping↗
PubMed1998

[A voluminous exteriorized odontogenic keratocyst].

The authors report the case of a 63 years old man who presented a voluminous exteriorized keratocyst of the jaw. We have first made a punction of the cyst in order to facilitate the operation. Anatomopathological examination of the liquid found epithelial cells. We collected the keratocyst by a non interrupting mandibulotomy via cervical incision.

Humans↗
PubMed1997

Structure and specific expression of a Nicotiana sylvestris putative amino-acid transporter gene in mature and in vitro germinating pollen.

We report here the structure and expression analysis of a Nicotiana sylvestris gene, called nsaap1, coding for a protein which shows significant identity to the members of the Arabidopsis thaliana amino acid permease family. The nsaap1 gene is expressed exclusively in binucleate pollen. Its transcripts begin to accumulate after first pollen mitosis and dramatically increase in mature pollen shortly before anthesis and during in vitro pollen germination. The nsaap1 5'-flanking region contains long regions homologous to the promoter region of the tobacco pollen specific eIF-4A8 translation factor. Our results support the occurrence of an amino acid remobilization in binucleate pollen. The nsaap1 gene could play a role in exchanges between the vegetative and the generative pollen cells.

Amino Acid Sequence↗
PubMed1994

[Cystic forms of primary bronchopulmonary cancers. Apropos of a case].

We report a case of primary broncho-pulmonary cancer presenting as a round, fine walled cyst. Based on the observations in this case, and from the data in the literature, we suggest the characteristics of the radiology and scanning which should enable the neoplastic aetiology to be suspected.

Cysts↗
PubMed1992

[Contribution of intra-operative measurement of intact parathormone in surgery for primary hyperparathyroidism].

Using a sensitive two-site immunoradiometric assay which detects intact parathormone (iPTH), we studied the decrease in peripheric and jugular plasmatic iPTH during surgical removal of abnormal parathyroid (s). In the next future, results of intact parathormone (iPTH) assay will be given in 45 minutes. In a prospective study of 33 patients operated on for hyperparathyroidism or for cold thyroid nodule, the serum levels of intact PTH was measured intraoperatively in peripheric and in jugular blood. The preoperative mean serum iPTH concentration was 119.23 +/- 172.48 pg/ml and fell to 34.5 +/- 32.21 pg/ml after surgery in 14 cases of primary hyperparathyroidism (p < 0.001). Thirteen out of 14 patients had serum iPTH values less than 65 pg/ml within 15 minutes after parathyroidectomy. The preoperative mean serum iPTH concentration in the 5 secondary hyperparathyroidism was 781.2 +/- 403.19 pg/ml. This value fell to 124 +/- 66.91 pg/ml after parathyroidectomy (p < 0.04). No significant decrease was observed in the mean serum concentration of the 14 patients operated on for cold thyroid nodule. Patients suffering from single parathyroid adenoma presented a significant gradient in jugular plasmatic PTH concentration between the adenoma side and the contralateral one. This gradient decreased during effective parathyroid adenomectomy (309.7 +/- 313.3 pg/ml to 3.7 +/- 35.1 pg/ml). Intraoperative serum iPTH concentration will provide a valuable tool to appreciate the effectiveness of surgical removal of parathyroid glands and to detect the location of parathyroid adenoma when the surgical research is negative.

Adult↗
PubMed1990

[Subcutaneous avulsion of the flexor digitorum profundus and flexor digitorum superficialis tendons of the ring and little fingers caused by blast injury].

The authors report a case of subcutaneous avulsion of flexor profundus and flexor superficialis tendons of the ring and little finger, caused by a blast injury. Treatment consisted of excision of the flexor superficialis tendon with transosseous reinsertion of the flexor profundus tendon. The functional result was good. Subcutaneous traumatic rupture of flexor tendons occurs infrequently, but simultaneous rupture of both flexor tendons is extremely rare. Knowledge of the subject is limited and treatment of this disorder is poorly defined.

Adult↗
PubMedDate not supplied

[Pseudomonas aeruginosa septicemia. Host-related risk factors in 82 episodes].

OBJECTIVES: The prognosis of septicaemia due to Pseudomonas aeruginosa is severe with mortality ranging from 32 to 73%. We retrospectively studied 82 episodes in order to determine whether risk factors could be identified. METHODS: Eighty-two episodes of Pseudomonas aeruginosa septicaemia, observed between 1986 and 1991, were analyzed. Risk of death within 2 days of the first positive blood culture (mortality = 19.5%) were assessed with univariate and multivariate analyses. RESULTS: Patient age ranged from 1 to 92 years. Most had been hospitalized in medical wards (49%) or intensive care units (28%) (NS). The type of septicaemia (several bacteria in 21%), the source of the infection (nosocomial in 78%), portal, predisposing factors (cancer, haematologic disease: 54%) and MacCabe index were not significantly correlated with risk of death at two days following first positive blood culture. With univariate analysis body temperature below 38,5 degrees C was significant (p = 0.007) for death at day 2 and appropriate antibiotic treatment after diagnosis was significant (p < 0.001) for absence of death on day 2. For multivariate analysis, chemotherapy and shock syndrome were significant (p = 0.005 and 0.09 respectively) for death at day 2 and appropriate antibiotic treatment was significant (p = 0.005) for absence of death on day 2. CONCLUSION: Antibiotic prescription appears to be the most easily controlled significant factor predictive of outcome in Pseudomonas aeruginosa septicaemia.

Adolescent↗