N-arginine dibasic convertase.
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Amino Acid Sequence↗
Biomedical subjects
T Foulon
Publications and source records attributed to T Foulon.
Sequence of the canine herpesvirus thymidine kinase gene: taxon-preferred amino acid residues in the alphaherpesviral thymidine kinases.
Multiple sequence alignments of evolutionarily related proteins are finding increasing use as indicators of critical amino acid residues necessary for structural stability or involved in functional domains responsible for catalytic activities. In the past, a number of alignments have provided such information for the herpesviral thymidine kinases, for which three-dimensional structures are not yet available. We have sequenced the thymidine kinase gene of a canine herpesvirus, and with a multiple alignment have identified amino acids preferentially conserved in either of two taxons, the genera Varicellovirus and Simplexvirus, of the subfamily Alphaherpesvirinae. Since some regions of the thymidine kinases show otherwise elevated levels of substitutional tolerance, these conserved amino acids are candidates for critical residues which have become fixed through selection during the evolutionary divergence of these enzymes. Several pairs with distinctive patterns of distribution among the various viruses occur in or near highly conserved sequence motifs previously proposed to form the catalytic site, and we speculate that they may represent interacting, co-ordinately variable residues.
Alphaherpesvirinae↗
N-arginine dibasic convertase, a metalloendopeptidase as a prototype of a class of processing enzymes.
N-Arg dibasic convertase is a metalloendopeptidase from rat brain cortex and testis that cleaves peptide substrates on the N terminus of Arg residues in dibasic stretches. By using both an oligonucleotide and antibodies to screen a rat testis cDNA library, a full-length cDNA was isolated. The sequence contains an open reading frame of 1161 codons corresponding to a protein of 133 kDa that exhibits 35% and 48% similarity with Escherichia coli protease III (pitrilysin, EC 3.4.99.44) and rat or human insulinase (EC 3.4.99.45), respectively. Moreover, the presence of the HXXEH amino acid signature (XX = FL) clearly classifies N-Arg dibasic convertase as a member of the pitrilysin family of zinc-metalloendopeptidases. In addition, a Cys residue that may be responsible for the thiol sensitivity of the insulinase and N-Arg dibasic convertase was proposed. The protein sequence contains a distinctive additional feature consisting of a stretch of 71 acidic amino acids. We hypothesize that this metalloendopeptidase may be a member of a distinct class of processing enzymes.
Amino Acid Sequence↗
N-arginine dibasic convertase (NRD convertase): a newcomer to the family of processing endopeptidases. An overview.
N-arginine dibasic convertase (NRD convertase) (accession number L27124) is a metalloendopeptidase from rat brain cortex and testis which cleaves peptide substrates on the N-terminus of arginine residues in basic doublets. Its predicted amino acid sequence contains the putative zinc binding motif HXXEH in a region which exhibits 35% and 48% similarity with E coli protease III (pitrilysin E.C 3.4.99.44) and rat or human insulinase (E.C 3.4.99.45) respectively. This feature clearly classifies this endopeptidase as a member of the pitrilysin family of zinc-metalloproteases. However, the NRD convertase sequence contains a distinctive additional feature consisting of a 71 acidic amino acid stretch. Its substrate selectivity and the characteristic motifs of its amino acid sequence allow us to propose this new metalloendopeptidase as the first member of a new class of processing enzymes.
Amino Acid Sequence↗
A bovine cell line stably expressing porcine tumor necrosis factor alpha (TNF-alpha): growth properties and permissivity for pseudorabies virus replication.
To explore the feasibility of modifying the pathogenicity of pseudorabies virus (PrV), we have undertaken a program to develop recombinant PrV carrying the porcine tumor necrosis factor alpha (TNF-alpha) gene. We have used a cloned genomic DNA fragment containing the entire porcine TNF-alpha gene (Chardon et al., 1991), and have deleted the 3' non-translated region which is supposed to be a tissue-specific regulatory sequence. We have also removed the 5' non-translated region containing a TATA-box and binding sites for other transcription factors. The resulting TNF-alpha cassette has been inserted into a neomycin-selectable shuttle vector. This construct has been used to select MDBK cell lines harbouring the TNF-alpha-carrying plasmids in order to verify the production of biologically active TNF-alpha. One cell line thus obtained secreted 20-30 pg/10(6) cells of active TNF-alpha after five days in culture and exhibited normal growth kinetics. PrV titers on this cell line were the same as titers on cells not expressing TNF-alpha, indicating that TNF-alpha expression in MDBK cells does not abrogate their permissivity for virus replication. Our results show that construction of recombinant PrV expressing TNF-alpha should be possible using the MDBK cell line as host.
Animals↗
Possible relation between the U54 segment of the CTHV genome and the conserved gene block C rearranged in alpha and gamma herpesvirus genomes.
The genome of CTHV is an atypical member of the gamma-2 subgroup of herpesvirus genomes that contains two segments (instead of one) of DNA with low G+C content flanked by highly repetitious DNA with high G+C content. The segments freely undergo polarity inversion with respect to one another. We have found nucleotide sequences in one of these segments, the U54 segment, whose putative translational products show clear similarity to two ubiquitous herpesvirus gene products, a single-stranded DNA binding protein and a protein of the helicase superfamily. These sequences are located within 5 kilobase pairs of the ends of the segment, suggesting that U54 may be related to a genetically defined entity (gene block C; Davison and Taylor (1987) J. Gen Virol. 68, 36-48) issuing from a previous sequence comparison of the gamma-1 genome of Epstein-Barr virus and the alpha genome of varicella-zoster virus.
Alphaherpesvirinae↗
[Screening in the school milieu, at 4 years old, for hypercholesterolemia].
Four-year-old schoolchildren with a positive family history for atherogenic dyslipidemia and/or clinical atheroma before 55 years of age were screened for hypercholesterolemia. Investigations included determination of serum levels of total cholesterol, triglycerides, HDL cholesterol, apolipoprotein A1, apolipoprotein B, and Lp(a); an agarose lipidogram; acrylamide gradient electrophoresis; and determination of LDL composition by ultracentrifugation. Normal values were defined as values under the 90th centile, i.e., 1.97 g/l for total cholesterol, 0.89 g/l for triglycerides, 1.36 g/l for LDL-cholesterol, and 1.26 g/l for apolipoprotein B. Among 3,565 children routinely evaluated at 4 years of age, 525 (16.2%) had a positive family history; of these, 72 underwent lipid investigations. Eight children (11%) had hypercholesterolemia type IIA, eight had a variety of lipid disorders, and 14 (20.6%) had increased Lp(a) levels as an isolated anomaly or concomitantly with an atherogenic dyslipidemia. Because Lp(a) is a cardiovascular risk factor independent from total cholesterol levels, we believe this parameter should be determined in high risk children.
Apolipoprotein A-I↗
Relationship of omega-3 fatty acid supplementation to plasma lipid peroxidation in predialysis patients with hypertriglyceridaemia.
OBJECTIVES: Since it has been suggested that omega-3 polyunsaturated fatty acids (PUFA) may be an efficient treatment for dyslipoproteinaemia and renal function in uraemic patients, this study was carried out to evaluate the potential adverse effects of polyunsaturated acids on lipid peroxidation in patients with chronic renal failure. PATIENTS AND METHODS: Five uraemic predialysis patients with various renal diseases presenting progressive renal failure and moderate hypertriglyceridaemia (1.93 +/- 0.60 g/L) in comparison with the reference values of our laboratory (0.88 +/- 0.20 g/L) were given 6 g of fish oil per day for 6 months in the form of Maxepa capsules containing a low dose of tocopherol acetate (10.5 mg/day). During the treatment we investigated the effect (expected to be beneficial) of n-3 PUFA on triglyceride plasma levels and renal function. We also investigated the potential side effect of such a treatment on lipid peroxidation. RESULTS: A moderate decrease of triglycerides early after the introduction of the treatment (1.93 +/- 0.6 g/L vs 1.33 +/- 0.58 g/L; 0 vs 0.5 months) was observed. In all patients, lipid peroxides measured as thiobarbituric acid reactants increased early after the introduction of the n-3 PUFA therapy (2.8 + 0.8 vs 3.76 +/- 0.15 mumol/L; 0 vs 0.5 months). Organic hyperoxides were significantly different in these patients compared with laboratory values, but they did not increase significantly during the treatment. CONCLUSION: It must be noted that polyunsaturated fatty acids should be used with caution in predialysis patients.
Adult↗
[Changes in plasma lipoproteins in adolescents with trisomy 21 in response to a physical endurance test].
In a previous study, the authors recorded a free fatty acids (FFA) concentration decrease in 11 Down's Syndrome (DS) subjects after an incremental maximal exercise until exhaustion. The aim of this study was to determine if lipid metabolism parameters in a group of DS subjects could be changed after an endurance training period prior to a sustained physical exercise test. After an "adapted" exercise programme, 6 healthy DS subjects, 4 boys and 2 girls aged from 16 to 22 years, performed a sustained exercise lasting 40 minutes on an cycle ergometer. They also compared their values with those taken from the data of laboratory for similarly aged normal subjects. The results of this trial indicate: (a) at rest: (i) a lipid metabolism that included normal level of triglycerides (Trig), but low level of total cholesterol (TC), (ii) a pathological pattern of lipoproteins: low level in high density lipoprotein (HDL), and high level in pré beta very low density lipoprotein (VLDL); (b) after an "adapted" exercise programme period concluding with a final test: (i) an approximate adjustment to normal lipid profiles: rise in HDL and fall in VLDL (ii) a rise of free fatty acids (FFA) between the start and the end of the test. It is noted that physical activity of an endurance type appears to have a favourable long term effect on some manifestations of this genetic disease and that, consequently, such endurance training may be promoted.
Adolescent↗
[Herpesviridae: classification and structure in 1991].
In 1981, herpesviruses were classified by the International Committee of Taxonomy of Viruses (ICTV, 1) inside the herpesviridae family. Progress in biotechnology and molecular biology during the last 10 yr, has permitted the characterization of new viruses and genomic structures. The objective of this paper is to collect the data found in the literature since 1981, to actualize the description of herpesviridae family.
Animals↗
[Contribution of molecular biology to the diagnosis of familial hypercholesterolemias in children].
The detection of children at high risk in families with a genetic form of hypercholesterolemia is important for acceptance of prevention under medical control. However, usual lipidic parameters are difficult to interpret during infancy. So we studied by a molecular biology approach 11 families presenting with syndrome of pure hypercholesterolemia where a defect of the LDL receptor (LDL-R) gene was suspected (Familial Hypercholesterolemia: FH IIa). Markers of the LDL-R gene (Restriction Fragment Length Polymorphism RFLP) were studied with intragenic probes. The segregation of the abnormal gene was studied in each family. Our results illustrate the limits of such an approach (its heaviness and the fact that, in 2 families, the analysis was not informative), but also its advantages: indeed, in 8 families, the diagnosis was established (particularly in one case at birth). Moreover in 2 families the LDL-R abnormality was excluded. In such case, as an alternative, the hypothesis of an apo B abnormality was envisaged. This differential diagnosis is interesting since it permits the choice of an adequate treatment.
Adolescent↗
Effect of an acute zinc depletion on rat lipoprotein distribution and peroxidation.
The aim of this study was to determine the extent to which zinc depletion leads to lipoprotein modifications by measuring both lipoprotein-fraction distribution and peroxidation in zinc-depleted rats. The animals were divided into three groups and fed for 8 wk a zinc-adequate diet (100 ppm) ad libitum (AL), a zinc-deficient diet (0.2 ppm) ad libitum (ZD), or a zinc-adequate diet according to the pair feeding method (PF). Trace-element status, tissular lipids, and lipoprotein-fraction study were performed. The MDA production by the lipoprotein fraction was measured before and after induced peroxidation. Cholesterol and phospholipids were increased in ZD rats. An important increase of VLDL and IDL was observed and a significant enhanced production of MDA by the LDL was related to zinc deficiency. From this observation, we may conclude that LDL fractions of ZD rats are more susceptible to induced oxidative damage. These results suggest that in zinc deficiency, the lipoprotein fragility is an aggravating factor of peroxidation and the dyslipoproteinemia may lead to an atherogenic risk.
Animals↗
Rapid detection of pseudorabies virus genomic sequences in biological samples from infected pigs using polymerase chain reaction DNA amplification.
The presence of the pseudorabies virus (PRV) genome in infected hosts has previously been studied by standard hybridization techniques, which showed the viral genome to be present at very low levels in infected tissues. The recently introduced polymerase chain reaction (PCR) procedure provides an alternative and rapid means of amplifying small quantities of specific DNA sequences. We applied this technique to a study of pigs infected by PRV. The sequence selected for amplification consisted of 222 base pairs lying in the gene coding for the glycoprotein gp50. We used a pair of 20-mer oligonucleotides flanking this sequence as primer and a cloned Stu-Nde fragment containing the sequence as target DNA. To avoid the tedious DNA extraction procedure we performed PCR directly on disrupted cells and detected specific amplification after 25 cycles of PCR with the thermostable Taq DNA polymerase. Amplified products were detected by gel electrophoresis directly. Nasal samples from experimentally and naturally infected pigs were tested by this PCR technique. When compared with tissue culture and serological tests, detection by gel electrophoresis of PCR amplified fragments provided excellent specificity and sensitivity. We concluded that PCR amplification will be a valuable tool for rapid diagnosis of PRV infection in pigs, taking less than 1 h to complete.
Animals↗
Restriction maps for the cottontail rabbit herpesvirus (CTHV) genome.
The sites for restriction endonucleases ApaI, BamHI and PvuII in the genome of the cottontail rabbit herpesvirus were localized. The physical mapping of the 150-kb DNA was facilitated by peculiarities of the genome structure, namely the presence of repetitive DNA and of invertible segments, and by the analysis of overlapping cosmid clones.
Animals↗
DNA-binding proteins induced by the cottontail rabbit herpesvirus CTHV.
Several new polypeptides were detected in cells infected with CTHV, a cottontail rabbit herpesvirus. All of them (Mr 150K, 110K, 93K, 83K, 75K and 35K) accumulated in the nucleus during the infectious cycle, and all except the 150K species bound to DNA-cellulose affinity columns in low-salt buffers. Polyclonal antisera prepared against the 35K DNA-binding protein also recognized the 75K species. Although the 75K protein could be detected earlier in infection than the 35K protein, late in the infectious cycle the latter increased to an abundance approaching that of cellular histones. Treatment of partially purified virions with a non-ionic detergent indicated that the 35K protein, but not the 75K protein, is a component of capsid/tegument structures. The anti-35K/75K serum did not cross-react with herpesvirus sylvilagus virion proteins, which, in an electrophoretic comparison, exhibited both similarities to and differences from the virion proteins of CTHV. Labelling of CTHV-infected cells with [32P]orthophosphate revealed the presence of phosphoproteins electrophoretically comigrating with the 93K, 83K, 75K and 35K proteins.
Animals↗
[Electrophoresis of serum lipoproteins in man and normal adult dogs. Remarks on experiments].
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Adult↗
[Lipid homeostasis in newborn infants during exchange transfusion for jaundice. Study of 24 cases].
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Exchange Transfusion, Whole Blood↗
[Effects of oral contraceptive preparations and smoking on lipoprotein repartition].
We studied the effect of oral contraceptives and smoking on the lipid profile of 251 women and 72 men, 20-29-year-old. In women, taking estroprogestatives, cholesterol, triglycerides, apoproteins AI and B were higher than in controls; HDL-cholesterol was not modified. Lipoprotein analyses in polyacrylamide gradient gel exhibited an increase of the HDL3 fraction at the expense of the HDL2 fraction, with a reduced LDL size. Smoking in addition to estroprogestative absorption accentuated these modifications and led to a decreased HDL-cholesterol (HDL2 fraction essentially), with an increased LDL-cholesterol. In men, smoking resulted in higher levels of total cholesterol, apoprotein B and LDL-cholesterol, without any significant change in LDL size, higher levels of triglycerides and lower level of the HDL2 fraction without any change in HDL-cholesterol. In women, smoking led only to an increase in triglycerides. In summary, analysis of the distribution of HDL subclasses and of LDL size showed an evolution towards a supposed more atherogenic lipid profile in women taking oral contraceptives associated or not with smoking, and in male smokers.
Adult↗