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Biomedical subjects

M Mahieu

Publications and source records attributed to M Mahieu.

32 records · Page 2Linked to original sources
PubMed1995

In vitro NCp7 enhancement of ribozyme-mediated cleavage of full-length human IL-6 mRNA.

We have previously shown that a ribozyme directed against human interleukin-6 (IL-6) mRNA is efficient in vivo, despite its poor activity in vitro on full-length IL-6 mRNA. We compared the effect of the nucleocapsid protein of HIV-1 (NCp7) on the ribozyme cleavage reaction of a long (1041 nt) and a short (19 nt) substrate IL-6 RNA in vitro. At a one to five molar ratio of the long substrate to ribozyme, almost no cleavage is observed after 30 min at 37 degrees C. The NCp7 protein significantly increases the catalytic activity of the ribozyme on this substrate (from 0 to 53% after 7 min at 37 degrees C), but not on the short one. A kinetic analysis of single turnover reactions performed with ribozyme in at least fivefold molar excess over substrate also lead to a stimulation (70-fold) of the reaction rate with long substrate, but not with the shorter one. Preferential increases of the catalytic activity on the long substrate suggests that the NCp7 protein prevents misfolding of RNAs.

Base Sequence↗
PubMed1995

Catalytic activity and stability of hammerhead ribozymes containing 2'-acetamido-2'-deoxyribonucleosides.

Hammerhead ribozymes may be of great therapeutic importance, since they can, in theory, be developed to cleave any undesired target RNA. In order to design ribozymes which are stable against endogenous RNases, we incorporated 2'-acetamido-2'-deoxynucleosides in the catalytic core of a hammerhead ribozyme. The 2'-acetamido function has, like the hydroxyl group, both proton donor and proton acceptor capacities, which seem to be crucial for efficient catalytic activity. However, the presence of 2'-acetamido-2'-deoxypyrimidine residues in the catalytic core caused a considerable drop in cleavage rate. Replacement of the purine residues led to complete loss of the catalytic activity. Surprisingly, these 2'-modifications showed no beneficial influence on the stability of the ribozymes against RNases present in cell culture supernatant containing 10% fetal calf serum.

Acetamides↗
PubMed1994

Construction of a ribozyme directed against human interleukin-6 mRNA: evaluation of its catalytic activity in vitro and in vivo.

We have designed a ribozyme (Rz) that cleaves human interleukin-6 (IL-6) mRNA in vivo. This Rz was tested in vitro, and was found to give expected size fragments. It was then incorporated into a mammalian expression vector containing the constitutive cytomegalovirus (CMV) immediate early promoter and transfected into human U amniotic cells (UAC). Cell clones that stably express this catalytic RNA have been obtained. Some of them displayed a marked reduction of tumor necrosis factor (TNF)-induced IL-6 production. Their reduced ability to express IL-6 was related to the amount of Rz they produced and to the extent of IL-6 mRNA cleavage as observed by a ribonuclease protection assay. These data provide a method to study further the role of IL-6 production in various biologic situations, and suggest the feasibility of developing Rzs directed against various cytokines to study their biologic role and mechanism of action.

Base Sequence↗
PubMed1989

[Spondylodiscitis disclosing bacterial endocarditis. Apropos of a case. Review of the literature].

The authors report a case of infectious spondylodiscitis revealing a staphylococcal endocarditis in a patient with a Carpentier aortic heterograft. This case, along with 60 descriptions from the literature, has enabled them to specify the characteristics of occurrence of endocarditis during a spondylodiscitis. The clinical factors in favor of this association are: a pre-existing cardiopathy, an oral port of entry, occurrence of other rheumatoid manifestations, even more the presence of complications of endocarditis. The laboratory factors in favor of an association are: discovery of an inflammatory anemia, of circulating immune complexes, of a cryoglobulinemia, of a rheumatoid factor, of hematuria. But it is mostly the demonstration of streptococcus in blood cultures and other samples that should be an indication to search for an endocarditis, the course of which dominates the prognosis.

Discitis↗
PubMed1984

Effect of surgical trauma on various aspects of the immune response in rats.

The effects of a standard laparotomy on different aspects of the immune response were studied in Wistar R/A rats. When the antigen was administered at the time of operation, antibody synthesis against sheep red blood cells (SRBC), a thymo-dependent antigen was significantly stimulated. The same phenomenon was observed when a soluble antigen extracted from SRBC was injected during the surgical procedure. On the contrary, late antibody production induced by formalinized Salmonella enteritidis or Escherichia coli lipopolysaccharide, two thymo-independent antigens, was reduced in operated animals. Cell-mediated immunity against SRBC was investigated by the radiometric ear index test described by Kostiala in 1977. Surgery did not alter the induction phase but suppressed the expression of the cellular immune response. Carrageenin-induced edema was inhibited in operated rats. These results show that surgical trauma acts differently on the various aspects of the immune response.

Animals↗
PubMed1983

Effect of surgical trauma on delayed type hypersensitivity.

There is no general agreement in the literature concerning the effects of surgery on delayed type hypersensitivity (DTH). Therefore, the effect of a standard laparotomy on DTH was studied in rats and measured by the ear index method of Kostiala. Surgery depresses significantly the ear index in animals challenged at the time of operation (2.35 +/- 0.24 vs 6.30 +/- 1.26) or 24 hr later (2.69 +/- 0.21 vs 4.34 +/- 0.64). There is no late rebound of the immune response. The reduction of ear index is not due to a delayed response of operated rats but is really a decrease of the peak response. Surgery seems to act on the early phase of the immune response.

Animals↗
PubMedDate not supplied

[Circulating anticoagulants excluding hemophilia. Multicenter survey undertaken under the aegis of the French National Society of Internal Medicine apropos of 207 cases].

A retrospective multicentre study, undertaken under the aegis of the French National Society of Internal Medicine, involved 200 subjects with acquired circulating anticoagulants; 130 were female and 77 were male; mean age was 45 +/- 23 years (range: 10 months to 80 years). Mean duration of follow-up was 23 months. In 130 subjects the anticoagulants were detected as a result of a systematic screening examination. The main overt clinical manifestations were haemorrhages, venous or arterial thrombosis and spontaneous abortion. Typing of the anticoagulant, performed in 166 cases, showed the presence of an antiprothrombinase in 141; this enzyme is not responsible for severe bleeding unless it is associated with other disorders of coagulation; less frequent were an anti-factor VIIIc (n = 16) and an anti-factor V (n = 2) anticoagulants. An underlying pathology was found in 172 subjects, including systemic lupus erythematosus (n = 60), induced lupus (n = 11), discoid lupus (n = 3), infection (n = 23), blood disease (n = 19), cancer (n = 15) and vasculitis (n = 15); other factors were pregnancy (n = 5) and medicines (n = 6). The anticoagulant disappeared spontaneously in 10 cases and in 33 of the 115 subjects treated. In subjects with lupus and in children under twelve years of age, an antiprothrombinase was regularly identified at typing.

Adolescent↗
PubMedDate not supplied

Changes in gastro-intestinal helminth species diversity in lambs under mixed grazing on irrigated pastures in the tropics (French West Indies).

The development of gastro-intestinal helminth diversity was monitored in lambs grazing alone or grazing with heifers in the ratio one heifer to four lambs. Five successive cohorts of lambs were studied from January 1994 to May 1996. Each cohort of lambs grazed irrigated pastures of Pangola grass for 4 months (from weaning to 6 months of age). A total of 50 lambs was necropsied and their worms counted and identified at the end of each grazing period. Four heifers were also necropsied on one occasion. Special attention was dedicated to the identification of the most pathogenic worm, i.e. Haemonchus spp. Malate dehydrogenase polymorphism in H. contortus was studied in order to evaluate changes between cohorts and between grazing managements. The species diversity was estimated by Shannon diversity indices (main species or all species). It was higher in the mixed grazing group than in the lambs that grazed alone. Diversity increased in successive cohorts. This was due in part to the acquisition of Cooperia spp. of cattle origin. The increase in diversity in the mixed grazing lambs corresponded to the lower faecal egg excretion and better weight gains recorded previously in that group. There seemed to be no cross-transmission of H. similis found in heifers and H. contortus harboured by lambs. The latter species was not morphologically or genetically different in the lambs grazed alone or with heifers, indicating that the presence of cattle did not modify qualitatively the transmission of H. contortus.

Animal Feed↗