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Biomedical subjects

F Brunel

Publications and source records attributed to F Brunel.

At least 19 recordsLinked to original sources

Nuclear receptors Nor1 and NGFI-B/Nur77 play similar, albeit distinct, roles in the hypothalamo-pituitary-adrenal axis.

Studies in Nur77-deficient mice have shown that the basal regulation of hypothalamic and pituitary functions as well as the adrenocortical steroidogenesis in these animals is normal. This indicates that Nur77-related orphan receptors may substitute Nur77 functions in the hypothalamo-pituitary-adrenal axis by a compensatory mechanism. Nor1 is the most recently cloned member of the NGFI-B/Nur77 subfamily, and its properties are still largely unknown. We demonstrate here that Nor1 is expressed in the pituitary gland and adrenal cortex, and that ACTH and angiotensin II (AngII) treatment of adrenal fasciculata cells induces Nor1 expression. Time-course analysis with both hormones on steroidogenic capacity and the specific gene expression in adrenal cells strongly suggest that Nor1 is an intermediate in the long-term consequences of ACTH or AngII treatment. The Nor1 and NGFI-B/Nur77 amino acid sequence homology and the analysis of the trans-activation properties of Nor1 show that the overall structural and functional organization of the two proteins is similar. As observed with NGFI-B/Nur77, Nor1 activates the expression of genes encoding steroidogenic enzymes as P450c21, through its interaction with NGFI-B response element promoter sequences. In contrast, binding experiments of Nor1 with the palindromic NurRE sequence suggest that Nor1 is not an efficient substitute for the NGFI-B/Nur77 activation of the POMC gene expression in pituitary glands. All these results indicate that Nor1 and NGFI-B/Nur77 may play similar albeit distinct roles in the hypothalamo-pituitary-adrenal axis. Further experiments also show that the mechanisms responsible for the transcriptional regulation of Nor1 in adrenal cells appear to depend on the protein kinase A and protein kinase C cascades.

Adrenal Cortex↗

[Orbital complications of sinusitis in adults].

Orbital complications of sinusitis are rare in adults but delayed diagnosis is vision and life threatening. We report our experience in 6 patients to present clinical history, bacteriology and discuss the modality of treatment. There were 4 young men and 2 women, aged from 16 to 79 years old. Only one patient had an immunocompromised underlying condition (HIV infection). Four patients had preseptal abscesses and three post septal cellulitis or abscess (one patient had preseptal abscess and post septal abscess and hematoma). Two patients had a complete unilateral loss of light perception. Pathogens encountered were Streptococcus species: 4, strict anaerobes: 1, Pseudomonas aeruginosa: 1 (patient with AIDS). Patients recovered from infection with antibiotics in 6 and surgery in 5 but sequellar blindness occurred in 2 patients. Our experience emphasizes the necessity of antibiotic treatment in bacterial sinusitis and importance of early diagnosis and appropriate management of complications.

Abscess↗

Cationic lipid DC-Chol induces an improved and balanced immunity able to overcome the unresponsiveness to the hepatitis B vaccine.

Th1 and Th2 immune responses against antigens can be modulated by the use of adjuvants. Since antibody isotypes (IgG1 and IgG2a) and cytokines induced may reflect the Th differentiation taking place during the immune response, the humoral and cellular immune responses induced in mice against hepatitis B virus surface antigen (HBsAg) were examined when the antigen was either adsorbed to aluminum hydroxyde or administered with a new adjuvant the cationic lipid 3beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol). The use of DC-Chol increased antibody responses in responding BALB/c mice, induced more consistent IgG1 and IgG2a antibody responses in OF1 mice and overcame the nonresponse to HBsAg in B10.M mice. Furthermore, DC-Chol was able to induce cellular immune responses to HBsAg. The DC-Chol induced a balanced Th1/Th2 response, which enabled mice to overcome the inherited unresponsiveness to HBsAg encountered with aluminum-adjuvanted vaccine. Thus, the DC-Chol provides a signal to switch on both Th1 and Th2 responses, which may have important implications for vaccination against hepatitis B virus, as well as for enhancing weak immunogenicity of other recombinant purified antigens in a nonresponder population.

Adjuvants, Immunologic↗

The polypyrimidine tract binding (PTB) protein interacts with single-stranded DNA in a sequence-specific manner.

Polypyrimidine tract binding (PTB) protein is a cellular factor whose function is unknown. Various RNA or single-stranded DNA sequences have been shown to interact with PTB. In this paper, using laser UV crosslinking and electrophoretic mobility shift assays to probe DNA-protein interactions, we demonstrate that PTB binding at a single-stranded DNA target is highly sequence-specific. We provide data showing that PTB interacts with the top strand of the adenovirus major late promoter transcriptional initiator, a sequence rich in pyrimidine residues. We also demonstrate that PTB is organised into at least two different binding domains.

Adenoviridae↗

Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression.

Unliganded human thyroid hormone receptor alpha (hTR alpha) can repress transcription by inhibiting the formation of a functional preinitiation complex (PIC) on promoters bearing thyroid hormone receptor (TR)-binding elements. Here we demonstrate that hTR alpha directly contacts the TATA-binding protein (TBP) and that preincubation of hTR alpha with TBP completely alleviates TR-mediated repression in vitro. Using stepwise preassembled PICs, we show that hTR alpha targets either the TBP/TFIIA or the TBP/TFIIA/TFIIB steps of PIC assembly for repression. We also show that the repression domain of hTR alpha maps to the C-terminal ligand-binding region and that direct TR-TBP interactions can be inhibited by thyroid hormone. Together, these results suggest a model in which unliganded hTR alpha contacts promoter-bound TBP and interferes with later steps in the initiation of transcription.

Amino Acid Sequence↗

The upstream stimulatory factor functionally interacts with the Alzheimer amyloid beta-protein precursor gene.

The amyloid beta-protein precursor (APP) gives rise to the A beta peptide, which is deposited in the brains of patients with Alzheimer's disease and Down's syndrome. Overexpression of APP due to a third copy of the gene appears to correlate with very early onset of Alzheimer's disease neuropathology in the brains of Down's syndrome patients. Thus, the identification of the factors involved with transcriptional regulation of the APP gene could provide critical clues regarding the events leading to the formation of amyloid deposits. An overlapping AP-1/AP-4 site in the proximal promoter region (-39 to -49) of the human APP gene has previously been shown to increase transcription 4-fold. Here we identify the factor binding specifically to this element as the upstream stimulatory factor USF, unrelated to the c-fos/c-jun complex or the AP-4 factor. In vitro transcription and co-transfection studies show that USF activates transcription from the APP promoter and that the AP-1/AP-4 element participates in this activation. Modulation of APP expression via regulation of USF could potentially ameliorate the production of Alzheimer-augmented beta-amyloid.

Alzheimer Disease↗

[The Ko phenotype and fetal-maternal allo-immunization].

BACKGROUND: Very few people have no Kell antigens (phenotype Ko). They can develop antibodies to Kell antigens after transfusion, or the abortion of a Kell-positive fetus. This paper describes a case of immunization that may have been due to amniocentesis. CASE REPORT: The eighth pregnancy of a woman required an amniocentesis on the 17th week for chromosomal study because she was 41 years old. She had 4 prior abortions. Her blood group was A Rh+. Her red cells were not tested for rare blood groups and antibodies to blood groups were not screened before and after amniocentesis. The newborn baby developed hemolytic anemia. On her 10th hour of life, her hemoglobin was 10.7 g% and her bilirubinemia 308 mumol/l. Her blood group was A Rh+. Indirect Coomb's test was positive in the mother, and the baby was given 3 exchange transfusions of O+, Ccee, K- blood. Further studies showed that the mother had phenotype Ko (A+, Ccce, K-, k-, Kpa-, Kpb-, Jsa-, Jsb-). The baby's phenotype was K-, k+, Kpa-, Kpb-, Jsa-, Jsb+. The mother was found to have a high titer of Ku antibodies. CONCLUSION: This mother belongs to one of the 3 families known in the Reunion Island to have phenotype Ko. She had never been given transfusions, and prior abortions are unlikely to have played a role since no hemolysis was seen in further newborns. While amniocentesis is probably a major factor, its role cannot be determined because no pre-amniocentesis samples were analysed immunologically.

Amniocentesis↗

[Tracheal neurinoma simulating status asthmaticus in a child].

BACKGROUND: Neurilemmoma is a benign tumor that is rarely located in the trachea. A neurilemmoma in the intrathoracic part of the trachea can mimic severe status asthmaticus. CASE REPORT: A 14 year-old girl was admitted because of persistent signs of status asthmaticus, despite bronchodilator therapy. She had no history of asthma. A worsening of the wheezing while she was in the intensive care unit led to intubation and respiratory support. X-rays showed pneumomediastinum. A dramatic improvement only followed replacement of the intratracheal tube. On the 5th day of the disease, tracheoscopy showed a sessile tumor obstructing two-thirds of the lumen, 3 cm above carena. Biopsy showed the tumor to be a neurilemmoma; it was excised. Scar tissue developed and was responsible for stenosis; it required laser therapy and an endotracheal prosthesis. Neither the girl nor her parents showed signs of neurofibromatosis. CONCLUSIONS: An intrathoracic tracheal tumor can produce asthmatoid wheezing. A definitive diagnosis can be made only by tracheoscopy.

Adolescent↗

[Hepatic abscess due to Yersinia in a child with thalassemia].

A 15-year-old boy with thalassaemia major treated with desferrioxamine, experienced fever associated with digestive disorders. These symptoms led to the discovery of multiple liver abscesses. Therapy included antibiotics (third generation cephalosporin and aminoglycoside) and desferrioxamine discontinuation. Recovery occurred within one month approximately. Systemic yersiniosis was further confirmed by the finding of antibodies to Yersinia enterocolitica O5. The systemic diffusion of Yersinia is favoured by iron-overload and iron-chelating agents.

Adolescent↗

Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients.

Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation.

Adolescent↗

Cloning and sequencing of Pseudomonas genes determining sodium dodecyl sulfate biodegradation.

The nucleotide sequences of two genes involved in sodium dodecyl sulfate (SDS) degradation, by Pseudomonas, have been determined. One of these, sdsA, codes for an alkyl sulfatase (58,957 Da) and has similarity (31.8% identity over a 201-amino acid stretch) to the N terminus of a predicted protein of unknown function from Mycobacterium tuberculosis. The other gene, sdsB, codes for a positive activator protein (33,600 Da) that has extensive similarity with the lysR family of helix-turn-helix DNA-binding activator proteins.

Amino Acid Sequence↗

Cloning and sequencing of PYBP, a pyrimidine-rich specific single strand DNA-binding protein.

In the human transferrin gene promoter, PRI and DRI are positive cis-acting elements interacting respectively with two families of proteins, Tf-LF1 and Tf-LF2. In this paper, we report the purification from rat liver nuclei, of one of these factors, PYBP, as well as the cloning and the sequencing of its cDNA. PYBP is a DNA-binding protein, purified as a 58 kDa doublet which binds only to single strand pyrimidine-rich DNA present for example in PRI and DRI. The protein binds also to a similar polypyrimidine tract present in one of the two strands of a DNA regulatory element of the rat tyrosine aminotransferase gene enhancer. PYBP gene is transcribed ubiquitously as a roughly 2.8 kb RNA which is likely to be subject to an alternative splicing. PYBP is highly homologous to a mouse nuclear protein, as well as to PTB, its human version, which interacts specifically with the pyrimidine tracts of introns. Primary structure information and predicted secondary structure elements of the protein indicate that PYBP contains four sequence repeats. Each of these repeats appears to exhibit the typical RNA recognition motif found in several proteins interacting with RNA or single strand DNA. Finally several hypotheses concerning the biological function of PYBP are presented.

Amino Acid Sequence↗

[Spinal cord injuries in infants in traffic accidents].

The authors report on three cases of spinal cord injury in 11, 14 and 21-month-old infants, involved in motor vehicle accidents. Neurologic lesions were caused by a forcible flexion of the head over a fixed trunk. Pathomechanics management problems and therapeutic considerations are discussed.

Accidents, Traffic↗

[Removal of two calcium hydroxide preparations: S.E.M. study].

Calcium hydroxide is one of the most often medication used for temporary treatment in endodontics. Different forms of preparation are available. The aim of this study is to evaluate in vitro the elimination of the pharmaceutical and the commercial forms of presentation. The aspect of the dentinal walls were analysed using SEM and X-ray microanalysis. The results show that Ca(OH)2 removal is difficult but there is no significant difference of elimination between the two forms.

Calcium Hydroxide↗

[Determination of apolipoproteins B in children: use in the screening of atherogenic risk and influence of diet].

The determination of plasma concentrations of apolipoproteins B (apo B) among 390 children (age 2-18 years) and the study of their antecedents showed that the prevalence of family histories of ischaemic cardiovascular diseases was higher among children whose apo B reached or exceeded 1.20 g/l. A low cholesterol diet was prescribed for children whose apo B levels were equal to or higher than 1.20 g/l. Two years later 45 of them were re-examined: they showed decreased apo B levels and a significant relationship between the magnitude of the decrease and the dietetic score related to the observance of the diet.

Adolescent↗

Bacteriophage T7 RNA polymerase-controlled specific gene expression in Pseudomonas.

The rifampicin (Rif)-resistant RNA polymerase of phage T7 has proved invaluable for the exclusive over-expression, in Escherichia coli, of genes cloned downstream from the T7 phi 10 promoter [Tabor and Richardson, Proc. Natl. Acad. Sci. USA 82 (1985) 1074-1078]. Here, we demonstrate that the system can be extended to Gram-negative bacteria other than E. coli, by the use of compatible wide host range plasmids. As an example, the Rif-resistant in vivo synthesis and specific radiolabelling of E. coli galactokinase in Pseudomonas ATCC19151, is demonstrated. The incidental observation that 30 min after treatment with Rif, two polypeptides continue to be synthesized in plasmid-free Pseudomonas ATCC19151, indicates that these proteins are produced by very stable mRNA species.

Cloning, Molecular↗