Search PubMed⌕ Search

Biomedical subjects

C Perret

Publications and source records attributed to C Perret.

At least 145 records · Page 8Linked to original sources

17 beta-estradiol stimulates the calbindin-D9k (CaBP9k) gene expression at the transcriptional and posttranscriptional levels in the rat uterus.

The 9 kilodalton vitamin D-dependent calcium-binding protein (CaBP9k), calbindin-D9k, is expressed in the intestine and uterus of mammals. Rat intestinal CaBP9k is a well documented expression of the steroid hormone like action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). In contrast exogenous 1,25-(OH)2D3 does not affect the concentration of uterine CaBP9k which is dependent on estrogen. We have analyzed the effect of 17 beta-estradiol on the regulation of CaBP9k gene expression in the uterus of mature ovariectomized rats. CaBP9k mRNA is undetectable in the uterus of mature ovariectomized rats. A single dose of 17 beta-estradiol results in a detectable level of CaBP9k mRNA at 1 h and a significant increase 3 h after injection. The maximal CaBP9k mRNA level is reached 6 to 12 h post injection. These results show that 17 beta-estradiol increases CaBP9k production by increasing CaBP9k gene transcription. Chronic 17 beta-estradiol administration results in a plateau of CaBP9k mRNA but in a large increase in CaBP9k concentration. The kinetic response to a single estradiol injection was similar in immature rats. This result shows that no cellular differentiation is required for the control of CaBP9k gene expression by 17 beta-estradiol. The uterine cells of immature rats are already competent to respond optimally to estradiol. There is a single 0.5 kilobase CaBP9k gene transcript in the rat duodenum. In contrast there are two estrogen-inducible CaBP9k mRNA species in the uterus of both the mature ovariectomized and the immature rats. The smallest species corresponds to the duodenal CaBP9k mRNA species, while the larger species is at least 50 nucleotides larger. However, a unique CaBP9k identical to that in the duodenum is expressed in the uterus.

Animals↗

[Structure, expression and control of calbindins-D].

The Calbindins-D (CaBP9K and 28K), like calmodulin, belong to a group of intracellular proteins that bind calcium with high affinity. Each protein is encoded by a separate gene and there is no direct filiation between the two genes. We have demonstrated the tissue-specific expression and regulation of CaBP9K gene. This gene is expressed in the intestine, placenta and uterus of the rat as a single 0.5kb long transcript. Exogenous 1,25(OH)2D3 triggers the rapid synthesis of CaBP9K mRNA and accumulation of translatable CaBP9K mRNA in the duodenum of vitamin D-deficient rats. Calcium also stimulates CaBP9K gene expression in this tissue. In contrast 1,25(OH)2D3 does not change the uterine concentration of CaBP9K but estrogen stimulates the transcription of the CaBP9K gene in the uterus. The promoter region of rat CaBP9K gene contains 1 TATA box and 4 CAAT box-type sequences and several steroid hormone regulatory elements. The CaBP9K gene is therefore a suitable model for studying the tissue-specific regulation of gene expression by steroid hormones.

Animals↗

Acute heart failure in myocardial infarction: principles of treatment.

Congestive heart failure after acute myocardial infarction can extend the area of infarction by worsening the oxygen supply-demand balance. Appropriate treatment requires insight into this pathophysiologic condition and knowledge of the effects of the various therapies available. Understanding of the role of vasodilating and inotropic agents and of mechanical interventions such as ventilation with PEEP is an important aspect of treatment.

Acute Disease↗

Cloning and analysis of calbindin-D28K cDNA and its expression in the central nervous system.

The vitamin D-dependent calcium-binding protein (CaBP), calbindin-D28K (CaBP28K), is present in the central nervous system (CNS), the sensory system, and kidneys of mammals and birds. Recent studies have indicated that several other CaBPs of very similar Mrs are also present in the CNS. This study was carried out to establish the relationship between CaBP28K and other CaBP, particularly spot 35, to provide a basis for further studies on the tissue-specific regulation and distribution of CaBP28K. A cloned pC28 cDNA was isolated from a rat brain expression library using synthetic oligodeoxyribonucleotides (oligos) complementary to rat spot-35 mRNA. This pC28 cDNA had an open reading frame (ORF) of 783 nucleotides (nt) coding for a 261-aa, 30-kDa protein. There was 100% homology between the pC28 sequence and that of the CaBP28K isolated from rat brain cDNA library using a chicken intestinal CaBP28K probe (Hunziker and Schrickel, 1988). Thus the aa and nt sequences of rat CaBP28K and spot 35 are identical. Primer extension studies and Northern analyses show that the major species of CaBP28K mRNA contains a 5'-untranslated region of 132 nt, a coding region of 261 codons and a 3'-untranslated region of 804 nt without the poly(A) tail. The rat CaBP28K probe hybridizes to one major RNA species (1.9 kb) and two minor ones (2.8 and 3.2 kb) in the cerebellum, hippocampus, retina and kidney. This distribution correlates well with the distribution of CaBP28K itself in these organs. Comparison of the genomic organization of the CaBP28K gene with that of other members of the 'EF-hand' CaBP family emphasizes that the CaBP28K gene diverged from the others at the first duplication of the gene encoding one CaBP domain. All the members of the 'EF-hand' gene CaBP family evolved by exon shuffling and specific genomic rearrangements.

Amino Acid Sequence↗

Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells.

To determine whether endothelin, a highly potent vasoconstrictor peptide, may affect cardiac myocyte contractility directly, we studied the effects of synthetic porcine endothelin-1 in cultured chick embryo ventricular cells. Endothelin-1 had a potent chronotropic effect (EC50 0.17 nmol/l) in spontaneously beating cells. The increase in the beating rate was accompanied by a frequency-dependent decrease in the amplitude of contraction. In electrically driven cells (1 Hz), endothelin-1 increased the amplitude of contraction dose-dependently, with an EC50 of 0.3 nmol/l, smaller than that of the calcium channel blocker BAY K 8644 (EC50 3.3 nmol/l), and with an efficacy close to that of BAY K 8644 and isoproterenol. Nicardipine (100 nmol/l) shifted to the right, by two orders of magnitude, the dose-response curve of endothelin-1 for inotropism. These results indicate that endothelin-1 is one of the most potent inotropic agents in cultured cardiac myocytes, and suggest that this effect involves, at least in part, a calcium ion influx through voltage-sensitive calcium channels.

Animals↗

Time constant histograms from the forced expired volume signal: a clinical evaluation.

We evaluated a multicompartment analysis of forced expiration, based on modelling the lung as a set of twenty parallel compartments emptying exponentially with time constants ranging from 0.1-10 s; the forced expired volume signal was represented by a histogram showing the fraction of forced vital capacity as a function of compartmental time constants. We applied this technique to 80 healthy and 12 asthmatic subjects. The histograms computed from three consecutive forced expirations were poorly reproducible in 18 of the 80 healthy and 2 of the 12 asthmatic subjects. In the asthmatics, the time constant histograms conveyed no additional information on bronchial obstruction, beyond that already present in standard spirometric indices. A simulation study showed a high sensitivity of the histograms to the truncation of the terminal part of forced expiration. We conclude that the usefulness of the time constant histogram technique appears doubtful.

Adult↗

[The treatment of acute cardiac insufficiency: toward a physiopathological approach].

The development of new inotropic or vasodilator agents, with different spectra of action makes possible a physiological approach to the treatment of acute cardiac failure. The choice depends on the functional disturbances measured and is then adapted to the response obtained. In the most serious cases, where pharmacological treatment proves insufficient, there need be no hesitation in using invasive methods which were formerly reserved for the treatment of cardiogenic shock. Systematic application of therapeutic formulae gives way to rational selection of the agent best adapted to the particular conditions brought about by a specified cardiopathy in a given patient.

Acute Disease↗

The rat vitamin-D-dependent calcium-binding protein (9-kDa CaBP) gene. Complete nucleotide sequence and structural organization.

The structural organization of the entire rat vitamin-D-dependent calcium-binding protein (9-kDa CaBP) gene was determined by analysis of overlapping genomic clones isolated from a rat genomic library using the rat 9-kDa CaBP cDNA [Desplan C., Heidmann O., Lillie J., Auffray C. and Thomasset M. (1983) J. Biol. Chem. 258, 13502-13505]. These clones together span 30 kbp of rat genomic DNA, with the rat 9-kDa CaBP gene lying in the middle. The 9-kDa CaBP gene is 2.5 kbp long and contains three exons interrupted by two introns. The first exon contains almost the entire 5' untranslated region. The second exon codes for the calcium-binding site I, the third exon codes for site II and the 3' untranslated region. Therefore each of the calcium-binding domains is encoded by single, separate exons. The transcription initiation site was identified by S1 nuclease mapping and primer extension. A consensus sequence TATAAA is localized 31 bp upstream from the cap site and the 'CCAAT-box' lies upstream from the transcription start. Single (AC)25 and (AG)23 repeats are present in the second intron together with an Alu-like sequence. Repetitive elements are present 5 kbp upstream from the cap site and in the 3' flanking region. Comparison of the known rat CaBP sequences (9-kDa CaBP, 28-kDa CaBP, S100 protein) shows that the 9-kDa CaBP is more closely related to the S100 protein than to the 28-kDa CaBP. There is no evidence to indicate that 9-kDa CaBP has arisen from the 28-kDa CaBP.

Amino Acid Sequence↗

Evolution of the EF-hand calcium-binding protein family: evidence for exon shuffling and intron insertion.

The evolutionary history of the intracellular calcium-binding protein superfamily is well documented. The members of this gene family are all believed to be derived from a common ancestor, which, itself, was the product of two successive gene duplications. In this study, we have compared and analyzed the structures of the recently described genes coding for these proteins. We propose a series of evolutionary events, which include exon shuffling and intron insertion, that could account for the evolutionary origin of all the members of this superfamily. According to this hypothesis, the ancestral gene, a product of two successive duplications, consisted of at least four exons. Each exon coding for a peptide (a calcium-binding domain) was separated by an intron that had mediated the duplication. Each distinct lineage evolved from this ancestor by genomic rearrangement, with insertion of introns being a prominent feature.

Amino Acid Sequence↗

[Report on the conservative treatment of melanoma of the uvea at the Lausanne University Ophthalmologic Clinic].

A great number of techniques are currently available for the conservative treatment of uveal melanomas: ocular applicators emitting gamma rays 60Co, 125I) or high-energy beta rays (106Ru/106Rh), light photocoagulation, surgical excision, and accelerated proton beam irradiation. Life expectancy following conservative treatment is equal to or better than that following enucleation. This is demonstrated by nonrandomized comparative studies, and by the authors' own long-term results following the conservative treatment of melanomas by 60Co applicators: mortality due to metastases of small melanomas was 3% (V = smaller than 10 x 10 x 3 mm), with medium-size melanomas it was 12% (V = 10 x 10 x 3-15 x 15 x 5 mm), and with large melanomas 21% (V = larger than 15 x 15 x 5 mm). Accelerated proton beam irradiation of uveal melanomas is currently the method of choice for the conservative treatment of uveal melanomas. The sharp boundaries of the irradiated zone, the uniformly distributed irradiation dose, and beam-splitting are the main advantages of this technique. During the last three years, 310 cases of uveal melanoma have been treated in Switzerland with an accelerated proton beam. Of these, 214 were followed up for more than one year. Eight patients (3.9%) died of metastases. Visual acuity was identical or superior to initial visual acuity in 60.3% of the cases, while 39.6% exhibited a deterioration of vision or a functional loss. Favorable results achieved by conservative treatment of uveal melanomas considerably limited the indications for enucleation, which is now only performed in exceptional situations.

Brachytherapy↗

Site of airway obstruction: effects on the acoustic impedance of excised pig lungs.

We investigated the relationship between the site of airway obstruction and the frequency dependence (FD) of lung acoustic impedance (ZL). The real (RL) and imaginary (XL) parts of ZL were measured by forced random noise in excised left pig lungs, before (base line) and after 1) no airway obstruction (controls, n = 10), 2) insufflation of 1-mm (B1, n = 5) or 2-mm (B2, n = 7) beads, and 3) partial reversible obstruction of lower lobar (LL) and then main-stem (MS) bronchus (n = 4). The beads caused both partial and total obstruction of airways with internal diameters of 2 mm (B1) and 2-6 mm (B2). Compared with base line, a negative FD of RL appeared from 4 to 10 Hz in LL, B1, and B2 obstructions. The FD of XL greater than 20 Hz increased in MS and LL obstruction exclusively and was the ZL feature that most clearly differentiated central from peripheral obstruction. In this experimental model, the anatomic limit distal from which obstruction no longer causes the "central" type of ZL change lies in airways with internal diameters notably greater than 2 mm.

Acoustic Impedance Tests↗

Respiratory acoustical impedance: a new technique to measure airway response during bronchial inhalation challenges.

Respiratory acoustical impedance, a new method to measure airway obstruction during quiet breathing, was compared with plethysmography and spirometry in 19 asthmatics undergoing a bronchial inhalation challenge with an allergen. Respiratory acoustical impedance and plethysmography were both more sensitive than spirometry in detecting bronchoconstriction. Respiratory acoustical impedance is easily measured during quiet breathing, even in uncooperative subjects; forced expirations, which may alter bronchial tone, are avoided. Respiratory acoustical impedance is sensitive and reliable in measuring acute airway obstruction.

Acoustic Impedance Tests↗

Transcriptional and post-transcriptional regulation of vitamin D-dependent calcium-binding protein gene expression in the rat duodenum by 1,25-dihydroxycholecalciferol.

Regulation of the expression of vitamin D-dependent calcium-binding protein (Mr 9000 CaBP) gene by 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in the rat duodenum. In vivo stimulation of Mr 9000 CaBP synthesis was analyzed using a complementary DNA probe and by measuring the rate of Mr 9000 CaBP gene transcription in isolated nuclei (run-on assay). A single 1,25-(OH)2D3 injection (650 pmol/100 g of body weight) induced a 2-fold increase in Mr 9000 CaBP gene transcription within 15 min in the duodenum of vitamin D-deficient rats. RNA synthesis was maximal at 1 h, then decreased until 16 h of postinjection. There was an initial transient accumulation of Mr 9000 CaBP mRNA (from 7 to 15 min), which was followed by a second, significant increase, by 3 h which remained elevated until 16 h. The magnitude and time course of the Mr 9000 CaBP increase was similar to that of its mRNA as early as 1 h after 1,25-(OH)2D3 administration. Mr 9000 CaBP gene transcription was not significantly induced by 1,25-(OH)2D3 in vitamin D-replete rats and no transient accumulation of Mr 9000 CaBP mRNA was observed. Thus, 1,25-(OH)2D3 modulates Mr 9000 CaBP gene expression in at least two ways, a rapid transcriptional stimulation and a post-transcriptional effect preventing degradation of Mr 9000 CaBP transcripts and accounting for their accumulation several hours after the hormone treatment.

Animals↗