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Biomedical subjects

D Denis

Publications and source records attributed to D Denis.

At least 55 records · Page 3Linked to original sources
PubMed1995

DNA synthesis generally initiates outside the simian virus 40 core origin in vitro.

The nucleotide positions at which DNA synthesis initiates in vitro, in the vicinity of the simian virus 40 origin, have been determined. Start sites for DNA synthesis are greatly suppressed over the simian virus 40 core origin. Relatively weak start sites are detected over the 21-bp repeats and T-antigen-binding site I; distal to these regions, stronger start sites are detected. Thus, studies using a model system for eukaryotic DNA replication indicate that DNA synthesis events initiate, in general, outside the core origin.

Base Sequence↗
PubMed1995

Effects of strabismus surgery on refraction in children.

We assessed 115 eyes of 59 children with esotropia 2-3 months postoperatively to evaluate the effects of strabismus surgery on refraction. Three variables were measured: spherical equivalent, and cylinder power and axis. The mean changes in spherical equivalent were non-significant. The axis of postoperative astigmatism moved towards 'with-the-rule', thus improving refraction. The amount of recession and the consequent changes in cylinder power were inversely related. The results showed a significant change in cylinder axis after recession of the inferior oblique. Recession-tucking procedures led to the largest changes in cylinder power.

Astigmatism↗
PubMed1994

Rat preadipocyte adenylyl cyclase: influence of fat localization and androgenic status.

The influence of androgenic status on basal and stimulated cAMP production, adenylyl cyclase activities and immunoblot quantified GS alpha and Gi alpha 2 subunits of the adenylyl cyclase regulatory proteins were compared in confluent preadipocytes from subcutaneous (SC) and deep-intraabdominal (epididymal) fat deposits. Maximal cAMP response to isoproterenol was lower in SC than in epididymal preadipocytes. After castration, this site-specific difference was suppressed. cAMP response to 2-chloroadenosine, which was identical in the two types of preadipocytes, was decreased by castration in epididymal cells but not in SC cells. The catalytic activity of adenylyl cyclase and its maximal response to GTP were higher in epididymal than in SC preadipocytes. This response to GTP was decreased by castration in epididymal preadipocytes while it remained unchanged in SC preadipocytes. The catalytic activity of adenylyl cyclase was unchanged by androgenic status whatever the cell localization. Levels of GS alpha quantified by immunoblotting were not modified whatever the androgenic status and cell origin. Levels of Gi alpha 2 were not affected by the androgenic status as well, but were lower in SC than in epididymal cells. This study shows that components of the adenylyl cyclase system in preadipocytes are differently regulated by the androgenic status depending on the anatomical origin of the cells.

Adenylyl Cyclases↗
PubMed1994

Long-term (3 years) prevention of trabecular postmenopausal bone loss with low-dose intermittent nasal salmon calcitonin.

The long-term effect of intermittent low-dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow-up to a previously published study. Randomized controlled group comparison was made of 287 healthy women with 6-36 months of natural menopause and no treatment interfering with calcium metabolism at an outpatient clinic for research in bone and cartilage metabolism. The 287 women were randomly allocated to 3 years of treatment with either 500 mg/day, 5 days/week of calcium or the same amount of calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of 186 women complied with the study protocol throughout. The main outcome measures were bone mineral density of the lumbar spine (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in bone mineral density after 36 months showed a positive (p < 0.05) outcome (1.8 +/- 5.7%; mean +/- SD) in the group treated with salmon calcitonin and calcium and a significant (p < 0.01) loss (-5.8 +/- 4.8%) in patients receiving calcium alone. The difference between the evolution of the two groups was significantly (p < 0.01) different after 6 months of treatment and remained so until the end of the study. No significant changes were recorded in biochemical parameters reflecting bone turnover. As previously shown during a 1 year follow-up, nasal salmon calcitonin given at low dose and intermittently, in association with calcium, can counteract trabecular postmenopausal bone loss.

Administration, Intranasal↗
PubMed1994

Ocular findings in trigonocephaly.

BACKGROUND: Trigonocephaly, caused by premature closure of the metopic suture, is a rare form of craniosynostosis. The aim of this study was to assess the visual outcome in children operated on for trigonocephaly. METHODS: We present eight cases of children with trigonocephaly surgically corrected by the same craniofacial technique. CT with 3D reconstruction was performed in all cases. Genitori defined three types of trigonocephaly according to the severity of the deformity of the skull base only types II and III were included in this study directed at evaluation of the ocular disorder. A complete eye examination was performed on all children by the same observer, with a follow-up of 2-6 years. RESULTS: 3D-CT reconstruction of the skull base showed that the frontozygomatic region was affected by the deformation. Ocular examination showed considerable astigmatism in most children with late operation. A low degree of strabismus was observed in most children. CONCLUSION: This study demonstrated that reconstructive surgery should be performed by the age of 6 months, given the immaturity of the visual system up to that time. Close cooperation between neurosurgeons, pediatricians and ophthalmologists is of paramount importance in order to prevent this bone deformation exerting an adverse effect on visual development. The ophthalmologist must possess a basic understanding of the various craniosynostoses.

Astigmatism↗
PubMed1994

Refractive error and ocular motility in plagiocephaly.

Plagiocephaly, which is caused by premature closure of one of the coronal sutures, leads to fronto-orbital asymmetry. The aim of this work was to study the repercussions of orbital deformation on the visual system. Twenty-one patients presenting with plagiocephaly at birth and operated on by the same craniofacial technique (bilateral approach with translation and advancement of the entire involved orbits) were included in the study. All of the patients were examined by clinical anthropometry with three-dimensional reconstruction and underwent complete eye examination by the same observer. Follow-up after craniofacial surgery ranged from 15 months to 4 years. In the last few years, three-dimensional reconstruction has shown that the anatomic region affected by the deformation is the frontozygomatic region and has thus made it possible to advance to another theory on the origins of ocular problems. The severe effect of orbital anomalies on the development of the visual system (binocular vision, strabismus with amblyopia, refractive errors) has been emphasized in the literature. The present study shows that the scheduling of reconstructive surgery is fundamental and must not exceed 6 months, given the immaturity of the visual system up until this time. This means that the ophthalmologist must be able to recognize the various craniostenoses in order to schedule reconstructive surgery as soon as possible. Cooperation between the neurosurgeon and the ophthalmologist is of paramount importance if the pathogenic effects of this bone deformation are to be stopped and proper visual development preserved.

Astigmatism↗
PubMed1994

The skull base in plagiocephaly.

Between 1975 and 1992, 426 children with craniofacial malformations were treated in the Department of Pediatric Neurosurgery at the Hôpital des Enfants de la Timone in Marseille. Plagiocephaly was present in 71 (16.6%). The authors present a reproducible analysis of the skull base in plagiocephaly based on these 71 patients. A control group of Mediterranean children (n = 20) was used for comparison. Clinical anthropometric patterns were analyzed in all cases. Comparison with the control group showed a difference only in the nasion-lambda distance. Data obtained from clinical anthropometry were compared for the involved and the uninvolved sides. A three-dimensional reconstruction was possible in 20 cases. The statistical correlation between the basal angles (nasion-pterional, nasion-petrosal, nasion-clino-basion, and zygomatic angles) of the involved and uninvolved sides allows a new nosographic identification of this complex malformation.

Cephalometry↗
PubMed1994

Mapping initiation sites for simian virus 40 DNA synthesis events in vitro.

Primer RNA-DNA, a small (approximately 30-nucleotide) RNA-DNA hybrid molecule, was identified in recent studies of simian virus 40 DNA synthesis in vitro. The available evidence indicates that primer RNA-DNA is the product of the polymerase alpha-primase complex. Primer RNA-DNA is formed exclusively on lagging-strand DNA templates; it is synthesized initially in the vicinity of the simian virus 40 origin and at later times at sites progressively distal to the origin. To further characterize initiation events, template sequences encoding the 5' ends of both primer RNA and primer DNA, formed during a 5-s pulse, have been determined. Analyses of these sequences demonstrate the existence of an initiation signal for lagging-strand synthesis. At any given position, the initiation signal is located within those template sequences encoding primer RNA, situated proximal to the nucleotide encoding the 5' end of the RNA primer. In most instances, the sequence 5'-TTN-3' (where N encodes the nucleotide at the 5' end of the primer) is a feature of the initiation signal. Initiation signals are present, on average, once every 19 nucleotides. These results are discussed in terms of the mechanism of Okazaki fragment formation and possible links between prokaryotic and eukaryotic initiation events.

Base Sequence↗
PubMed1993

Substituted thiopyrano[2,3,4-c,d]indoles as potent, selective, and orally active inhibitors of 5-lipoxygenase. Synthesis and biological evaluation of L-691,816.

Thiopyrano[2,3,4-c,d]indoles are a new class of 5-lipoxygenase (5-LO) inhibitors. SAR studies have demonstrated that the thiopyran ring, the 5-phenylpyridine substituent, and an acidic functional group on a four-carbon C-2 side chain are all required for optimal inhibitor potency. In contrast, the indolic nitrogen may be substituted with a variety of lipophilic groups. As a result of the SAR investigation, 44 (L-691,816; 5-[3-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy ]- 4,5-dihydro-1H-thiopyrano[2,3,4-c,d]indol-2-yl]-2,2-dimethylpro pyl]-1H- tetrazole) has been identified as a potent inhibitor of the 5-LO reaction both in vitro and in a range of in vivo models. Compound 44 inhibits 5-HPETE production by both rat and human 5-LO and LTB4 synthesis in human PMN leukocytes (IC50s 16, 75, and 10 nM, respectively). The mechanism of inhibition of 5-LO activity by compound 44 appears to involve the formation of a reversible deadend complex with the enzyme and does not involve reduction of the nonheme iron of 5-LO. Compound 44 is highly selective for 5-LO when compared to the inhibition of human FLAP, porcine 12-LO, and also ram seminal vesicle cyclooxygenase. In addition, 44 is orally active in a rat pleurisy model (inhibition of LTB4, ED50 = 1.9 mg/kg; 8 h pretreatment) as well as in the hyperreactive rat model of antigen-induced dyspnea (ED50 = 0.1 mg/kg; 2-h pretreatment). Excellent functional activity was also observed in both the conscious allergic monkey and sheep models of asthma. In the latter case, the functional activity observed correlated with the inhibition of urinary LTE4 excretion.

Administration, Oral↗
PubMed1993

Acute biochemical variations induced by four different calcium salts in healthy male volunteers.

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG'), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%; p < 0.01) increases in Ca and significant suppression of PTH (-37.4% to -57.4%; p < 0.01). Comparison of response curves revealed significantly (p < 0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG' and CC. No significant variation of iCT was recorded during the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Primer-DNA formation during simian virus 40 DNA replication in vitro.

Studies of simian virus 40 (SV40) DNA replication in vitro have identified a small (approximately 30-nucleotide) RNA-DNA hybrid species termed primer-DNA. Initial experiments indicated that T antigen and the polymerase alpha-primase complex are required to form primer-DNA. Proliferating cell nuclear antigen, and presumably proliferating cell nuclear antigen-dependent polymerases, is not needed to form this species. Herein, we present an investigation of the stages at which primer-DNA functions during SV40 DNA replication in vitro. Hybridization studies indicate that primer-DNA is initially formed in the origin region and is subsequently synthesized in regions distal to the origin. At all time points, primer-DNA is synthesized from templates for lagging-strand DNA replication. These studies indicate that primer-DNA functions during both initiation and elongation stages of SV40 DNA synthesis. Results of additional experiments suggesting a precursor-product relationship between formation of primer-DNA and Okazaki fragments are presented.

Antigens, Neoplasm↗
PubMed1993

Analytical and statistical survey of early stages of open-angle glaucoma with low luminance visual field.

The purpose of this study was to show the early visual field signs in glaucoma using the 'Moniteur Ophtalmologique' at a background mesopic luminance of 0.3 apostilbs. Forty-five patients were selected, and 68 eyes with suspected early glaucoma were examined. Among the defects which were studied, we noticed a predominance of what we called pericaecal scotoma (PCS) and levelling. These two first signs appear as an alarm signal. To detect the early visual field signs of open-angle glaucoma developing, this study recommends the use of a background mesopic luminance of 0.3 apostilbs and observation for two uncommon visual field signs: PCS in evolution around the blind spot and a slight decrease in central mesopic sensitivity called levelling.

Adult↗
PubMed1993

Walker-Warburg syndrome: a report of 3 cases.

Walker-Warburg syndrome is a congenital malformation syndrome of unknown etiology which is characterized by fatal neurological lesions. It was first described by Walker in 1942 as involving agyria, hydrocephalus and eye malformations. Its etiology has been discussed in all of the articles on the subject in the literature, but the majority of the authors describe it as an autosomal recessive syndrome. Ultrasonography plays a key role in detecting a cephalic anomaly by prenatal diagnosis as in our 2 cases. The aim of this article is to report 3 new cases of Walker-Warburg syndrome in two families. Knowledge of this syndrome emphasizes both the need for ultrasonographic observation and genetic counselling for families at risk.

Abnormalities, Multiple↗
PubMed1993

Ocular growth in the fetus. 1. Comparative study of axial length and biometric parameters in the fetus.

The knowledge of ocular growth during fetal life, when compared with other fetal biometric parameters, could not only provide a better definition of malformation syndromes but could also give a better understanding of certain pathological processes in premature babies and in newborns. As the literature concerning prenatal ocular dimensions contains few data, the aim of this study was to measure the axial length of the globe (AL) in fetuses and compare this measurement with their gestational age, weight, height, head circumference (HC) and thoracic circumference (TC) in order to compile a reference table. In the present study, 76 globes from 38 fetuses (18-41 weeks gestational age) from the Department of Pathology (Timone University Hospital, Marseille) were examined. Ultrasonography A and B were used to measure the AL, and a pathological examination determined fetal weight, HC, TC and height. We were interested to find out which of the parameters studied would give the best correlation with ocular growth. Statistical analysis showed that HC remained the most discriminant factor and correlated best with ocular growth. We thus obtained an equation for ocular size according to HC that could serve as a basis for detecting pre- or postnatal ocular defects.

Anthropometry↗
PubMed1993

Ocular growth in the fetus. 2. Comparative study of the growth of the globe and the orbit and the parameters of fetal growth.

In a previous study, we showed that the growth of the eye during fetal development compared with the other parameters of the fetus was above all connected to the head circumference, which appeared to be the most discriminant measurement. In a second study, we measured the growth of the orbit of the fetus in order to compare it with the growth of the globe and the cranial circumference. Another 60 eyeballs of 30 fetuses of 18-41 weeks gestational age were examined. The corneal diameter (CD) of the cornea was a measurement added to those used in the method in the previous study, and orbital radiography was carried out: the parameters used were the same as in the previous study measured in relation to the CD, orbital diameter (OD) and the biparietal diameter (BPD). The aim of this study was to show the links between the variations in the measurements and to estimate them in relation to fetal growth. The results confirm those of the previous study, and this study also shows that, in estimating the head circumference, the OD and CD are the most accurate indicators. This study was also concerned with the BPD: the best correlation is obtained with the OD, which can be estimated accordingly from the BPD. Although the OD is not in an area studied by ultrasonography (highly dependent on the sectional plane), this study shows that it should perhaps be reconsidered in the prenatal diagnosis of orbital malformation. It would then be necessary to take into account not only the BPD but also the relationship between the OD and the BPD.

Anthropometry↗
PubMed1992

Investigation of the mechanism of non-turnover-dependent inactivation of purified human 5-lipoxygenase. Inactivation by H2O2 and inhibition by metal ions.

Human 5-lipoxygenase is a non-heme iron protein which is reported to be highly unstable in the presence of oxygen. The results of this investigation demonstrate that H2O2 generated during air oxidation of thiols is the main factor in non-turnover-dependent inactivation of purified recombinant human 5-lipoxygenase for the following reasons: catalase protects against oxygen-dependent inactivation of the enzyme in the presence of dithiothreitol; the active, stable enzyme can be prepared under aerobic conditions with the exclusion of dithiothreitol and contaminating metal ions; 10 microM H2O2 causes the rapid inactivation of the enzyme. The native (ferrous) enzyme is approximately seven times more sensitive to inactivation by H2O2 than the ferric enzyme, suggesting that the mechanism of inactivation involves a Fenton-type reaction of the ferrous enzyme with H2O2, resulting in the formation of an activated oxygen species. Purification of 5-lipoxygenase under aerobic conditions (no dithiothreitol) results in an increase in both the specific activity of the purified protein [up to 70 mumol 5(S)-hydroperoxy-6-trans-8, 11, 14-cis-icosatetraenoic acid (5-HPETE)/mg protein] and in the ratio of specific activity to enzyme iron content compared to enzyme purified under anaerobic conditions in the presence of dithiothreitol. The reaction of the highly active 5-lipoxygenase enzyme shows a dependence on physiological intracellular calcium concentrations, half-maximal product formation being obtained at 0.9 microM free Ca2+. The maximal enzyme activity is also dependent on EDTA and dithiothreitol and low amounts of carrier protein, as well as the known activators PtdCho and ATP. Ca2+ can be substituted by Mn2+, Ba2+ and Sr2+, although lower levels of stimulation are obtained. 5-Lipoxygenase is strongly inhibited by low concentrations (< or = 10 microM) of Zn2+ and Cu2+. The inhibition by Cu2+ is apparently irreversible, whereas that by Zn2+ is slowly reversed (t1/2 = 2 min) in the presence of excess EDTA. These observations on the mechanism of non-turnover-dependent inactivation of 5-lipoxygenase, and the optimisation of assay conditions, have facilitated the purification of large quantities of relatively stable enzyme that will be useful for further kinetic and physical studies.

Arachidonate 5-Lipoxygenase↗