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Biomedical subjects

A Fantoni

Publications and source records attributed to A Fantoni.

At least 37 records · Page 2Linked to original sources
PubMed1995

Molecular basis of estrogen regulation of Hageman factor XII gene expression.

Estrogen therapy has been reported to cause multiple alterations in hemostasis and to increase blood levels of several procoagulants, including Hageman factor [factor XII (FXII)]. Liver FXII gene expression has been investigated in ovariectomized rats, treated or not with 17 beta-estradiol. A 6-fold stimulation of FXII gene transcription was observed in treated compared to untreated animals, indicating that 17 beta-estradiol is able to induce FXII gene expression in vivo. We have recently shown that human FXII promoter contains an imperfect palindrome, 5'-GGGCAnnnTGACC-3', at position -43/-31 resembling the consensus estrogen-responsive element (ERE). Portions of different length of the FXII promoter were fused to the chloramphenicol acetyltransferase (CAT) coding sequence and transiently cotransfected with human estrogen receptor (ER) into NIH3T3 and HepG2 cells in the presence or absence of 17 beta-estradiol. A 230-base pair fragment of FXII promoter, spanning nucleotides - 181/49, conferred a strong estrogen responsiveness to the CAT reporter gene, suggesting that a functional ERE resides in this region. Cognate receptors, such as those for thyroid hormone or retinoic acid, did not stimulate CAT activity. Gel mobility assays demonstrated a specific interaction between ER and the 230-bp FXII promoter fragment containing the putative ERE palindrome. Similar results were obtained when an oligonucleotide spanning the consensus ERE was used; the complex between ER and FXII promoter sequences was supershifted after the addition of an anti-ER monoclonal antibody. Insertion of FXII-ERE into the heterologous thymidine kinase promoter conferred a strong estrogen responsiveness that was abolished by mutations of the 5'-half of the palindrome. These results represent the first demonstration at the molecular level of the regulation of a blood coagulation factor gene by 17 beta-estradiol as well as the first identification of a functional ERE within this class of genes.

Animals↗
PubMed1994

RNA polymerase III-mediated transcription of the trypanosome U2 small nuclear RNA gene is controlled by both intragenic and extragenic regulatory elements.

Transcription of U2 small nuclear RNA (snRNA) genes in eukaryotes is executed by RNA polymerase II and is dependent on extragenic cis-acting regulatory sequences which are not found in other genes. Here we have mapped promoter elements of the Trypanosoma brucei U2 snRNA gene by transient DNA expression of mutant constructs in insect form trypanosomes. Unlike other eukaryotic U2 snRNA genes, the T. brucei homolog is transcribed by an RNA polymerase III-like enzyme on the basis of its sensitivity to the inhibitors alpha-amanitin and tagetitoxin. Thus, the trypanosome U2 snRNA provides a unique example of an RNA polymerase III transcript carrying a trimethylated cap structure. The promoter of this gene consists of three distinct elements: an intragenic sequence close to the 5' end of the coding region, which is probably required to position the polymerase at the correct transcription start site; and two extragenic elements, located 110 and 160 nucleotides upstream, which are essential for U2 snRNA gene expression. These two elements closely resemble both in sequence and in distance from each other the A and B box consensus sequences of the internal control regions of tRNA genes.

Amanitins↗
PubMed1993

The 5' sequence of human factor XII gene contains transcription regulatory elements typical of liver specific, estrogen-modulated genes.

The human Factor XII gene codes for a serine proteinase synthesized in liver that activates both the coagulation and the fibrinolytic cascades. The nucleotide sequence analysis of a HincII-HincII 3129 bp fragment was performed showing that the FXII promoter region contains neither CAAT and TATA regulatory elements, nor GC islands, but revealing the presence of two tandemly repeated sequences in opposite orientation, two LF-A1 elements typical of the liver specific genes and one estrogen responsive element, that substantiates the observation of Factor XII gene modulation by estrogens.

Base Sequence↗
PubMed1992

Control of human coagulation by recombinant serine proteases. Blood clotting is activated by recombinant factor XII deleted of five regulatory domains.

The availability of engineered serine proteases allows one to study the activation, substrate specificity and regulation of human coagulation and fibrinolytic activities. Human coagulation factor XII is composed of the protease catalytic region at the C-terminus, a hinge proline-rich region and regulatory domains at the N-terminus. From cDNA clones coding for factor XII, two DNA molecules were constructed, one being full length and the other being deleted of exons coding for the regulatory domains. Engineered factor-XII cDNA species were inserted by a homologous recombination technique into vaccinia viruses, which were used to infect the human hepatoma cell line HepG2. Two recombinant proteins were prepared from the culture media and identified by their antigenic properties and electrophoretic mobilities. The recombinant protein of larger size was identified as the full-length factor XII of 80 kDa and its specific activities and activation patterns, determined both by the coagulation and the amidolytic assays, are very similar to these of native human factor XII. The recombinant protein of smaller size was identified as a 319-amino-acid-deleted factor-XII protein of 32 kDa, containing only the entire protease region and part of the proline-rich hinge. This protein was expected to be the 'minimal' portion of factor XII able to sustain protease but unable to recognize substrates and surfaces necessary to activate the contact phase of coagulation. However, this 'minimal' factor-XII protein displays a marked protease activity and, although lacking five regulatory domains of factor XII, is bound and activated by negative charges and promotes coagulation with high efficiency.

Base Sequence↗
PubMed1992

[Thoraco-abdominal binding in the treatment of overdistention of the lung bases in children].

In the patient with homogeneously or inhomogeneously distributed atelectasis, localized primarily in the apices, overdistension of the non-dependent portion of the lung bases, only partially surrounded by the rib cage, is generally observed during mechanical ventilation. This phenomenon is even more pronounced in the neonate and in the infant because their rib cage compliance is almost infinite. In order to protect the lung bases in the event of their overdistension and/or to reexpand the atelectasis of the upper lobes we apply an external resistance, in form of thoracoabdominal binding, to limit the movement of the diaphragm. The degree of the binding's tension is regulated according to the degree of the distension of the lung bases detected on chest x-ray. This restriction was so far applied in 12 children using elastic bandages. We have used the thoraco-abdominal binding with good result in the treatment of atelectasis of the upper lobes, in extensive atelectasis as well as in the treatment of primitive lung bases overdistension, as described in 3 cases reports. We suggest this technique in order to obtain an homogeneous ventilation along the longitudinal axis of the lung. This method does not interfere with prone-supine postural changes, systematically applied in our department, and therefore, the homogeneous ventilation along the vertical axis is also provided.

Abdomen↗
PubMed1990

Carrier detection for hemophilia B: evaluation of multiple polymorphic sites.

DNA analysis was performed in families with hemophilia B. Restriction fragment length polymorphisms (RFLPs) produced by endonucleases Taql, Xmnl, and Ddel were studied by two factor IX genomic probes, F9(VIII) and F9(XIII). Fifty-seven subjects from ten families were investigated; of them, 31 were carriers (11 obligate and 20 potential). Of the potential carriers, ten displayed laboratory features allowing for a phenotypic diagnosis of heterozygosity. Segregation analysis of the markers was informative in 19/20 potential carriers, which belong to nine of the ten studied families. Among the potential carriers, Taql allowed the carriership assessment in 15 (78.9%), Xmnl in 15 (94.7%), and Ddel in two (10.4%). Diagnosis was not possible in one family since a homozygosity in the key individuals with all the employed enzymes (Taql, Xmnl, Ddel, + BamHI) was found. Hemophilia B syndrome in two families likely results from a new mutation. In one family, a first-trimester prenatal diagnosis was performed. The use of RFLP analysis allowed us to improve genetic counseling as compared with the phenotypic evaluation by clotting factor assays. Indeed, evaluation of RFLP increased by 26% the carriership assessment of the potential carriers of the hemophilia B trait.

DNA Probes↗
PubMed1990

Effect of nifedipine on morphine-induced analgesia.

Experimental data show that opiates interfere with calcium influx in the cell and that some calcium-channel blockers are analgesic. We therefore studied the effect of the calcium-receptor blocker nifedipine on the analgesic effect of morphine in the rat, using tail-flick responses, and in humans, using measurements of the intensity of postoperative pain. In both the experimental animals and humans nifedipine significantly (P less than 0.001) increased the analgesic effect of morphine independently of any effect on the metabolism of morphine. Respiratory and cardiovascular functions were not significantly changed by nifedipine. The data indicate that Ca2+ is important in mediating the analgesic effects of opiates and suggest that calcium-receptor blockers might find a place in the treatment of pain.

Adult↗
PubMed1990

[Tumor marker ca. 125 in acute pelvic inflammations].

The paper reports a case of acute pelvic inflammatory disease (PID): the symptoms, diagnostic treatment and therapy, which was carried out according to standard protocols, the operation and the postoperative period were all fully correlated with serum concentrations of the marker ca. 125. Above all, a close interdependence was observed between the clinical regression of disease and the parallel reduction of marker serum levels. The graphic curve of ca. 125 was compared during the postoperative period to the curves expressed by the levels of GB and VES values. The method of monitoring highlighted the parallelism of the three curves with a particular affinity between the ca. 125 and GB curves.

Acute Disease↗
PubMed1990

[Clinical patterns of fibrocystic mastopathy in relation to parity and age].

Two thousand five hundred and twenty cases of fibrocystic mastopathy (FCM) were chosen from a vast population of patients examined during the period from 1980 to 1989. The main clinical symptoms of FCM were assessed in relation to their evolution according to age and parity. Correlations were observed between the clinical symptoms examined and the age range of patients. Parity was also significantly correlated to clinical symptoms of FCM.

Adolescent↗
PubMed1988

Assignment of human coagulation factor XII (fXII) to chromosome 5 by cDNA hybridization to DNA from somatic cell hybrids.

Human coagulation factor XII (fXII), a serine protease synthesized in liver and active in plasma, is involved in a wide variety of functions, including blood coagulation, fibrinolysis, bradykinin and complement activation. A complementary DNA (597 bp) encoding amino acid -16 to amino acid 183 of fXII protein was used to determine the chromosomal location of the fXII gene. DNAs from hamster-human somatic cell hybrids were digested with restriction enzymes and hybridized with the fXII cDNA. By the Southern method it was shown that restriction fragments able to hybridize to fXII cDNA are present only in DNA extracted from clones retaining human chromosome 5.

Animals↗