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Biomedical subjects

M Revel

Publications and source records attributed to M Revel.

At least 181 records · Page 10Linked to original sources
PubMed1987

[Sciatica caused by synovial cysts and lumbar articular diverticula with intraspinal development. Saccoradiculographic, computed tomographic and arthrographic study].

The authors report 8 cases of patients with synovial cysts (3 cases) or diverticuli (5 cases) of the lumbar joints, compressing the sciatic roots. They describe the radiological aspects of the two sides of the degenerative pathology of the posterior articular processes, which are relatively unrecognized (14 cases in the literature). They insist on the advantage of saccoradiculography which is the only test to be able to demonstrate dynamic alterations in relation with diverticuli, if performed in a standing position. The authors show the advantage of tomodensitometry which supports the diagnosis of cyst in the presence of a fibrous wall image. They emphasize the value of the arthrography of the posterior joint; it presents a diagnostic role by visualizing the cavities, and a therapeutic role by permitting the injection in situ of steroids and/or local anesthetics.

Aged↗
PubMed1986

Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines.

Induced human fibroblasts produce several mRNAs encoding interferon (IFN) activity. We previously cloned cDNA for a 1.3-kb RNA designated IFN-beta 2 and distinct from the 0.9-kb IFN-beta 1 mRNA. In vitro transcription--translation mapping of the full-length IFN-beta 2 cDNA sequence, shows that it encodes a 23.7-kd protein of 212 amino acids. This cDNA, fused to the SV40 early gene promoter, was transfected and amplified in Chinese hamster ovary cells and clones were obtained which constitutively produce human interferon activity. Two IFN-beta 2 genomic clones were isolated and their expression in hamster and mouse cells also produces biologically active rIFN-beta 2. Specific immunoassays show that IFN-beta 2 secreted by DNA-transformed rodent cells is a processed 21-kd protein, whose activity is cross-neutralized by antibodies to human IFN-beta 1 but not to IFN-alpha or gamma. The immunoassay also demonstrates the induction of IFN-beta 2 secretion by fibroblasts in response to growth-regulatory cytokines, such as interleukin-1 and tumor necrosis factor. The function of this IFN-beta 2 as an autoregulatory inhibitor of cell growth is discussed.

Animals↗
PubMed1986

Human chromosome 7 carries the beta 2 interferon gene.

A cDNA clone (pAE20-4) corresponding to the 1.3-kilobase human beta 2 interferon mRNA was used as a probe in blot-hybridization experiments of DNA from a panel of human-rodent somatic cell hybrids containing overlapping subsets of human chromosomes. The DNA hybridization experiments showed that the human beta 2 interferon gene is located on human chromosome 7. This assignment is consistent with previous experimental data in which the expression of the translationally active 1.3-kilobase beta 2 interferon mRNA was assayed in various somatic cell hybrids. Blot-hybridization experiments using DNA from different human cell strains and cell lines reveal distinct EcoRI restriction fragment length polymorphisms of the human beta 2 interferon gene.

Animals↗
PubMed1985

3' end structure of the human (2'-5') oligo A synthetase gene: prediction of two distinct proteins with cell type-specific expression.

Analysis of the sizes of the (2'-5') oligo A synthetase polyadenylated transcripts in various human cell lines by hybridization with a cDNA probe revealed that the pattern of the transcripts was cell-type specific. In order to investigate whether the 1.6 Kb, 1.8 Kb and 3.6 Kb mRNA, which are predominantly expressed in different cell-lines, encode different proteins or could differ in the size of their 3' or 5' untranslated sequences, the corresponding gene was isolated. On Southern blots of human genomic RNA, the cDNA probe hybridize to a 3.1 Kb EcoRI fragment. Three overlapping genomic clones were isolated which contain the same 3.1 Kb EcoRI fragment. Transcriptional mapping of the 3' end of the gene by Northern blots, hybridization translation experiments and sequencing showed that the 1.6 and 1.8 Kb mRNA are produced by a differential processing at the 3' end of the primary transcript of the same gene. The polyadenylation site of the 1.6 Kb mRNA is located 1.9 Kb upstream to the one of the 1.8 Kb mRNA. To produce the latter transcript, a portion of the last exon of the 1.6 Kb mRNA (including a segment coding for a very hydrophobic sequence of 18 amino acids and 3' untranslated sequence) is spliced out. The two mRNAs thus encode two different proteins which could have different affinity for cellular elements. The 3.6 Kb transcript has the same polyadenylation site as the 1.8 Kb mRNA, but contains additional unspliced 3' intron sequences.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Structure of two forms of the interferon-induced (2'-5') oligo A synthetase of human cells based on cDNAs and gene sequences.

The (2'-5') oligo A synthetase E, one of the translational inhibitory enzymes whose synthesis is strongly induced by all interferons (IFNs), is shown to be encoded in human cells by a 13.5-kb gene. By a cell-specific differential splicing, between the seventh and an additional eighth exon of this gene, two active E mRNAs of 1.6 and 1.8 kb are produced, along with several longer transcripts. cDNA clones for the two mRNAs were obtained and their sequences indicate that the human (2'-5') oligo A synthetase gene codes for two forms of the enzyme of mol. wt. 41 000 and 46 000, which differ only by their C-terminal ends. The product of the 1.6-kb RNA (E16) has a very hydrophobic C terminus, which is replaced by a longer acidic C-terminal sequence in the 1.8-kb RNA product (E18). The transcriptional start site of the gene was identified and 200 bp of the 5' flanking region were sequenced. A strong homology was found between this region of the IFN-activated (2'-5') oligo A synthetase gene and the corresponding region of the human fibroblast IFN-beta 1 gene, whose transcription is also stimulated by IFN priming. The gene has two polyadenylation sites which share a common undecanucleotide, but are used in a cell-specific manner to give rise to the 1.6- and 1.8-kb mRNAs.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Identification of viral infections in pregnancy by assay of (2'-5')-oligo-isoadenylate synthetase.

Interferons are produced in response to viral infections. Among the biochemical changes they cause in cells is the induction of the enzyme (2'-5')-oligo-isoadenylate synthetase. The activity of this enzyme can be measured and this can indicate exposure and response of cells to interferon. The efficacy of such an assay of peripheral blood of pregnant women may aid in establishing screening guidelines for potentially teratogenic viral infections. The blood of 44 primigravidas with complaints of fever, myalgia, cough, vaginal discharge and/or costovertebral angle tenderness was assayed for activity of the enzyme (2'-5')-oligo-isoadenylate synthetase and compared to assays of the enzyme activity in a group of 37 healthy primigravidas which served as a control group. It was found that the group with viral infections had an increase in enzyme activity from twice to 15 times the normal value, with characteristic rises of enzyme activity in several viruses known or suspected to cause human defects. Several general guidelines are proposed to assist the obstetrician in determining a viral etiology of acute illness in pregnancy, It is suggested that the assay of enzyme activity of (2'-5')-oligo-isoadenylate synthetase may provide a simple tool for rapid diagnosis of viral infections in pregnancy.

Adult↗
PubMed1985

Family of human alpha-interferon-like sequences.

An interferon-alpha-like sequence was isolated from a human genomic library by hybridization with a 15-base oligonucleotide. The sequence also showed homology to alpha-interferon and was most closely related to the leukocyte interferon-M gene fragment. The original isolate cross-hybridized to a family of sequences, 10 of which were isolated as clones. Some of these sequences were located within a few kilobases of alpha-interferon genes, consistent with our assignment of several members of the family to human chromosome 9 which also has the beta 1- and alpha-interferon genes.

Amino Acid Sequence↗
PubMed1985

Rapid improvement in a terminal case of hairy cell leukemia treated with a new human recombinant interferon, IFN-alpha-C.

A new type of human interferon (IFN), IFN-alpha-C, produced in Escherichia coli and purified on monoclonal antibodies, was given at a dose of 3 X 10(6) u (3 micrograms)/day to a terminally ill unsplenectomized patient with hairy cell leukemia, who had had severe recurrent infections and pancytopenia. There was marked reduction in the size of the spleen after 2 weeks, and platelet counts returned to normal after 1 month of treatment. The IFN treatment also raised the granulocyte counts and hemoglobin levels, improved the normal repopulation of the bone marrow, and restored resistance to infections. IFN-alpha-C was well tolerated, without serious side effects, and treatment has been continued for 10 months.

Cytotoxicity Tests, Immunologic↗
PubMed1984

A human IFN-beta 1 gene deleted of promoter sequences upstream from the TATA box is controlled post-transcriptionally by dsRNA.

Induction of IFN-beta 1 RNA was studied in the mouse cell line SR117-21E transformed by a BPV episome containing the human IFN-beta 1 gene deleted of promoter sequences upstream from position -40. Nuclei isolated from these cells synthesize constitutively IFN-beta 1 RNA from the partially deleted promoter. The IFN-beta 1 RNA synthesized by nuclei of uninduced SR117-21E cells is similar to that made by nuclei of poly(rI):(rC)-induced cells, but does not accumulate and hence no IFN is produced unless the cells have been treated either by ds RNA or by cycloheximide. We conclude that the IFN-beta 1 gene has, in addition to the transcription control due to upstream promoter sequences, an additional post-transcriptional control acting on mRNA accumulation and linked to sequences close to the TATA box and RNA start site. Both controls are relieved by ds RNA.

Animals↗
PubMed1984

Autogenous production of interferon-beta switches on HLA genes during differentiation of histiocytic lymphoma U937 cells.

The expression of class I HLA genes was measured during the in vitro differentiation of human U937 lymphoma cells towards macrophages. Following the onset of differentiation by phorbol myristate acetate the levels of cytoplasmic mRNA that hybridized with a [32P]HLA-B cDNA probe increased by a factor of nine. Elevation in HLA mRNA accumulation was followed by an increase in the rate of synthesis of HLA proteins and also by a dramatic increase in class I HLA cell surface antigen expression, as shown by cytofluorimetric analysis. The elevation in HLA mRNA and surface antigens could be prevented by adding antibodies against human interferon-beta (IFN-beta) to the culture medium at the onset of differentiation. Interferon antiviral activity was detected in the medium of differentiated U937 cells. The same anti-IFN-beta antibodies prevented the increase in (2'-5')oligo(A) synthetase activity which also takes place in differentiating U937 cells. Accumulation of the IFN-induced (2'-5')oligo(A) synthetase in U937 cells is preceded by an increase in its specific 1.6-kb mRNA as shown by hybridization to cloned (2'-5')-oligo(A) synthetase cDNA. The enzyme was preferentially found in the nuclear fraction of differentiating U937 cells. We suggest that an autogenous production of interferon-beta by the differentiating cells, switches on expression of the class I HLA genes as well as that of the (2'-5')oligo(A) synthetase.

2',5'-Oligoadenylate Synthetase↗
PubMed1984

Interferon-induced cytotoxicity and (2'-5') oligo(A) synthetase activity in T cells. Differences in responsiveness among T cells from various individuals and among lymphoblastoid T-cell lines.

Peripheral blood T lymphocytes became cytotoxic toward Daudi lymphoblastoid cells when incubated in vitro with interferon (IFN). The degree and rate of response to IFN varied markedly from one blood donor to another. "Low responders," who reproducibly showed a slower response to IFN, as well as "high responders" could be identified. The rate of increase in (2'-5') oligo(A) synthetase activity in IFN-treated cells also varied and appeared to correlate to the rate of increase in cytotoxicity. Three lymphoblastoid T-cell lines (Molt 4, Peer, HPB-ALL) also became cytotoxic towards Daudi cells when incubated with IFN and in these cells too the rate of induction of cytotoxicity appeared to correlate to the rate of increase in (2'-5') oligo(A) synthetase activity. Differences in responsiveness of T cells to IFN-mediated cytotoxicity might, therefore, reflect differences in responsiveness to IFN in general. Thus, quantitation of these differences might yield useful information for assessing the dosage and frequency of IFN administration to patients undergoing therapy.

2',5'-Oligoadenylate Synthetase↗
PubMed1984

Efficient constitutive production of human fibroblast interferon by hamster cells transformed with the IFN-beta 1 gene fused to an SV40 early promoter.

The coding sequence of the human interferon (IFN)-beta 1 gene, fused 60 bp downstream from the RNA start site of the SV40 early gene, was transfected into dihydrofolate reductase (DHFR)-deficient Chinese hamster ovary (CHO) cells together with a selectable DHFR gene. Most transformants continuously secreted IFN-beta 1 into the medium. Induction did not stimulate expression of the fused SV40-IFN-beta 1 gene. The role of the SV40 promoter was verified by transforming cells with the unmodified human IFN-beta 1 gene, or by the IFN-beta 1 coding region fused to another poly(rI):(rC)-inducible gene. In these cases, the transformants showed strictly inducible (not constitutive) IFN secretion. By selection for methotrexate resistance, CHO clones with a 10-20-fold amplification of the SV40-IFN-beta 1 DNA were obtained. Such clones constitutively produce up to 350,000 units IFN/ml per 10(6) cells/24 hr, i.e., over 10 times more than fully induced human fibroblasts. In continuous culture with daily changes of medium, accumulation of IFN-beta 1 is constant at a rate of 300,000 molecules per cell/hr. Batches of up to 16 mg of IFN-beta 1 produced by the transformed CHO cells were purified to homogeneity by affinity chromatography on monoclonal antibodies. This IFN appears identical in size, activity, and immunospecificity to the native human IFN-beta 1 glycoprotein.

Animals↗
PubMed1984

(2'-5') Oligo A synthetase in human polymorphonuclear cells increased activity in interferon treatment and in viral infections.

The interferon (IFN)-induced enzyme 2-5A synthetase was found in human peripheral blood polymorphonuclear cells (PMNL). The average enzyme activity in a group of 15 patients with various viral infections was significantly higher (25-fold) than in healthy individuals. Eight patients with multiple sclerosis and six patients with bacterial infections were found to have normal 2-5A synthetase levels in the PMNL. Relationship of PMNL 2-5A synthetase levels to IFN was confirmed by finding enzyme increases in PMNL incubated in vitro with IFN, as well as in patients undergoing IFN therapy. These findings suggest that in PMNL, as in other cells, the level of 2-5A synthetase can be regulated by IFN and can be increased as a result of IFN information in diseases.

2',5'-Oligoadenylate Synthetase↗
PubMed1983

The gene S promoter of hepatitis B virus confers constitutive gene expression.

The properties of the promoter of the hepatitis B surface antigen (HBsAg) were studied using recombinants containing either this promoter or the SV40 early promoter. Mouse L cells were transfected with these recombinants and the levels of gene expression obtained with the two promoters were compared. The level of expression of a cellular gene, the human fibroblast interferon gene, obtained with the HBsAg promoter was comparable to that obtained with the SV40 early promoter. Similarly when the HBsAg gene was controlled by the SV40 early promoter the level of HBsAg synthesis is in the same range as that observed with its own promoter. Together these results suggest that although the HBsAg gene codes for a structural viral protein, its expression is constitutive as for an early gene. The implications of these observations on the synthesis of HBV particles in vivo are discussed.

Animals↗
PubMed1983

Interferon-induced 56,000 Mr protein and its mRNA in human cells: molecular cloning and partial sequence of the cDNA.

Treatment of responsive cells by interferons (IFNs) induces within a few hours a rise in the concentration of several proteins and mRNAs. In order to characterize these IFN-induced mRNA species, we have cloned in E. coli the cDNA made from a 17-18S poly(A)+ RNA of human fibroblastoid cells (SV80) treated with IFN-beta. We describe here a pBR322 recombinant plasmid (C56) which contains a 400 bp cDNA insert corresponding to a 18S mRNA species newly induced by IFN. The C56 mRNA codes for a 56,000 dalton protein easily detectable by hybridization-translation experiments. The sequence of 66 of the carboxy-terminal amino-acids of the protein can be deduced from the cDNA sequence. IFNs-alpha, beta or gamma are able to activate the expression of this gene in human fibroblasts as well as lymphoblastoid cells. The mRNA is not detectable without IFN; it reaches maximum levels (0.1% of the total poly(A)+ RNA) within 4-8 hrs and decreases after 16 hrs.

Amino Acid Sequence↗