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J Torresani

Publications and source records attributed to J Torresani.

At least 19 recordsLinked to original sources
PubMed1992

Thyroid hormone generalized resistance.

The syndromes of thyroid hormone resistance may affect overall or only some tissues. The generalized resistance is an inherited disease which involves a familial eumetabolic or hypometabolic goiter, increased free thyroid hormones with normal or elevated plasma TSH levels; children may present mental retardation, deafness, short stature and delayed bone age. The disease is frequently misdiagnosed. In vivo and in vitro tests may be used to assess the diagnosis. The defect of increment of sex hormone-binding globulin after administration of T3 may be useful in the demonstration of the disease. Therapy uses high T4 or T3 doses in hypometabolic patients. The generalized thyroid hormone resistance could be linked to abnormalities at the T3 receptor and c-erb A gene level, as a consequence of different point mutations or deletions involving the hormone-binding domain.

Drug Resistance↗
PubMed1992

Retinoic acid decreases nuclear triiodothyronine receptor expression and impairs an early step of adipose differentiation in the thyroid hormone-sensitive mouse Ob 17 preadipocyte cell line.

In the murine preadipocyte cell line Ob 17, T3 is known to be necessary at an early step of adipose differentiation for the expression of late phenotypes [lipogenic enzymes such as malic enzyme, glycerol-3-phosphate dehydrogenase (GPDH), etc.] and not necessary for the expression of lipoprotein lipase (LPL), which emerges earlier, at growth arrest. These cells contain nuclear T3 receptors, which mainly belong to products of the c-erbA alpha gene and are down-regulated by T3. In this work, retinoic acid (RA) added to Ob 17 cells at growth arrest impaired morphological differentiation and the development of both late (malic enzyme and GPDH) and early (LPL) phenotypes regardless of whether T3 was added. T3 sensitized the cells to the inhibitory action of RA; the ED50 for GPDH activity was shifted from 0.5 microM to 3 nM in cells cultured with 1.5 nM T3. Later addition of RA (6 days after growth arrest) did not inhibit the differentiation. RA also brought out a marked and fast decrease in nuclear T3 receptors. This was observed whatever the stage of cell development and related to both a rapid decrease in the relative abundance of c-erbA alpha-related mRNA species and an increased disappearance rate, suggesting the involvement of pre- and posttranslational events. RA and T3 acted additively in decreasing the T3 receptor and c-erbA alpha mRNA levels. The effects of RA on T3 receptors were rapidly reversed after RA withdrawal; the reversal was large (75%) when RA was introduced at growth arrest and total when introduced later. The cell sensitivity to RA, considering the T3 receptors, was higher at growth arrest (ED50 for RA, 0.2 and 1.5 microM in assays with RA added at growth arrest and 5 days later, respectively). The results suggest intricated regulatory pathways between RA and T3 at an early step of adipose differentiation and also suggest that among different mechanisms through which RA may impair this differentiation, a decreased level of nuclear T3 receptors at an early period should play a role.

ATP Citrate (pro-S)-Lyase↗
PubMed1992

Site-specific anti-c-erb A antibodies recognizing native thyroid hormone receptors: their use to detect the expression and localization of alpha and beta c-erb A proteins in rat liver.

The cell-specific expression and tissue distribution of c-erbA proteins alpha and beta is still unknown. To address this problem, we prepared anti-peptide antibodies directed against epitopes of human (h) c-erbA, specific for the alpha or beta form of thyroid hormone receptors. The cDNAs coding for h c-erbA beta 1, alpha 1 and alpha 2 were transcribed and the mRNAs were translated in vitro in the presence of 35S-methionine, and then their reactivity with the antisera was evaluated. The antiserum anti-beta 62-81 immunoprecipitated only the beta 1 receptor. The antiserum anti-alpha 144-162 determined precipitation of both alpha 1 and alpha 2 proteins but not of the beta 1 receptor. Anti-alpha 2 431-451 produced a selective precipitation of alpha 2, and had no effect on alpha 1 or beta 1 receptor. In order to study the interaction of the antibodies with native T3 receptor we evaluated the binding of antibodies to rat liver T3 receptors by Sephacryl S300 chromatography: both antisera anti-beta 62-81 and anti-alpha 144-162 caused a partial shift of the labeled T3-receptor complex to a higher molecular form, while the antibody directed against c-erbA alpha 2 did not produce any significant shift. The anti-peptide antibodies were then immunopurified by affinity chromatography and used to immunolocalize the different forms of c-erb A proteins in adult and fetal rat liver, by a sensitive immunohistochemical technique. All 3 antibodies stained mainly the nuclei of the majority of adult liver cells. No staining was detectable when the original antiserum was deprived of anti-peptide antibodies by running through the affinity columns or when the antibodies were pre-absorbed with the homologous peptide. No significant staining was present in the liver from rat fetus.

Animals↗
PubMed1991

Production of rat Spot14 protein in Escherichia coli.

Hormonal, nutritional and developmental factors modulate, in rat lipogenic tissues, the transcription of the mRNA coding for a protein of unknown function, called Spot14 (S14). The corresponding protein has never been purified from tissues. In this paper, we describe the production of S14 in Escherichia coli. In the absence of available antibodies (Ab) directed against S14 protein, our strategy was to produce this protein by constructing two different recombinant expression vectors. The first recombinant plasmid produced a S14::protein A fusion which was easily purified and then rabbit Ab could be raised against it. The second expression vector directly produced S14. This expression was demonstrated by specific binding of polyclonal Ab directed against the fusion protein. These Ab also recognized a rat-liver protein sharing characteristics of S14.

Animals↗
PubMed1991

Triiodothyronine control of ATP-citrate lyase and malic enzyme during differentiation of a murine preadipocyte cell line.

In the Ob 17 preadipocyte cell line, during adipose differentiation, T3 amplified the progressive expression of two enzymes of the lipogenic pathway, ATP-citrate lyase (ATP-CL) and malic enzyme (ME) as previously described for fatty acid synthase (FAS) and fatty acid synthesis, and in the same time-period of development. However, the stimulation by T3 was sustained at late stages of differentiation whereas it declined in FAS studies. The stimulation was preceded by an increase in the relative abundance of the specific mRNAs. Two ME mRNA species were detected (21S and 27S) and found to be differently distributed. Their abundance was asynchronously increased by T3 with a predominant effect on the 21S species. Culture of the cells in a thyroid-hormone depleted medium prevented any significant increase of ME activity. Early inclusion of T3 largely restored ME development whereas late elimination of T3 only moderately impaired it. It is suggested that T3 plays a crucial role at an early step of adipose differentiation, this leading to an increased expression of a set of late adipose phenotypes such as several lipogenic enzymes.

ATP Citrate (pro-S)-Lyase↗
PubMed1991

Developmental and thyroidal regulation of the nuclear T3 receptors/c-erb A oncogene products in the Ob 17 preadipocyte cell line.

In a thyroid hormone-sensitive mouse preadipocyte cell line (Ob 17), the concentration of nuclear T3 receptors increases during differentiation in an insulin-independent manner and decreases by 50-60 p.cent after medium supplementation with physiological concentrations of T3. The down-regulation of T3 receptors implies both quantitative and qualitative changes. The preadipocyte T3 receptors were previously reported to be heterogeneous in gel filtration and in their reactivity towards rabbit antibodies raised against large erb A alpha peptides. This report shows that the receptor heterogeneity is not modified during cell development, whereas T3 mainly depletes the receptor species that are both the most retarded in gel filtration and preferentially recognized by c-erb A alpha-specific antisera. The c-erb A alpha-related T3 receptors which predominate in preadipocytes, are thus probably mainly involved in receptor depletion by T3. A similar T3 receptor half-life of 12-13 h was estimated after cycloheximide addition to cells at confluence or later in the differentiation phase with or without T3. This suggested that development, or T3, might have mainly affected the production of T3 receptors. In Northern hybridization studies, using alpha- or beta-type c-erb A cDNA probes containing the entire coding sequence, only alpha-type mRNAs were detected with a predominant band of 2.8 kbases and two fainter bands of about 5.5 and 6.0 kbases. The alpha-type mRNA abundance relative to beta-actin significantly increased during differentiation and decreased after T3 addition.

Adipose Tissue↗
PubMed1991

[Pathology of thyroid hormone receptors].

The syndrome of resistance to thyroid hormones may affect overall or only some tissues. The generalized resistance associates a familial eu or hypometabolic goiter, increased free thyroid hormones with normal or elevated plasma TSH levels. The inheritance of the disease is autosomal dominant in most of the patients. In vivo or in vitro tests may be used to assess the diagnosis. Therapy refers to high doses of T3 or T4. Pituitary resistance to thyroid hormones leads to hyperthyroidism with normal or high TSH levels. The treatment uses different TSH suppressive drugs. Peripheral resistance associates hypometabolism with normal T4-T3 secretion and needs high T3 doses for therapy. An inherited abnormality of T3 nuclear receptor seems to be the consequence of a mutant gene. Hypersensitivity to thyroid hormones associates hypermetabolism with low or normal free thyroid hormone levels and increased T3 nuclear receptors.

Drug Resistance↗
PubMed1991

[Retinoic acid reduces the expression of nuclear receptors of triiodothyronin and inhibits an early stage of the differentiation in the Ob 17 preadipocytic strains].

In the murine preadipocyte cell line Ob 17, T3 is known as being necessary at an early step of adipose differentiation for the expression of late markers, but not necessary for the expression of early markers. These cells contain nuclear T3 receptors (RT3) which are products of c-erb A alpha proto oncogenes, and are down-regulated by T3. In these cells, retinoic acid (AR) inhibits the adipose differentiation and the expression of early and late markers, and T3 sensitizes the cells to the inhibitory action of AR. We also show that AR down-regulates the expression of RT3 at both pre- and post-translational levels. This inhibition is dependent on AR concentration, a peculiar sensitivity to AR being observed at an early step of development.

Adipose Tissue↗
PubMed1990

A case of hypersensitivity to thyroid hormones with normally functioning thyroid gland and increased nuclear triiodothyronine receptors.

A 52-year-old male presented himself with tachycardia crises which appeared first during childhood, increased in frequency without goiter or exophthalmos. Cardiac and adrenergic diseases were excluded. The thyroid function was normal regarding T4, free T4 and T3, TBG, radioiodine uptake, TSH and T3 suppressibility; however the TSH response to TRH was decreased. The lymphocyte nuclear T3 receptor was found with an affinity close to that of normal volunteers (Ka: 1.42 x 10(10) M-1 vs 1.95 +/- 0.35 x 10(10) M-1) and a binding capacity markedly increased (9.9 vs 3.7 +/- 0.4 fmol T3/100 micrograms DNA). Pindolol was inefficient on the dysrhythmia which disappeared with carbimazole and relapsed after withdrawal of the antithyroid drug. Under carbimazole, the plasma T4 markedly decreased (27.7 +/- 3.6 nmol/l) but the patient remained euthyroid. The clinical course and the laboratory data suggest that the tachycardia crises are the consequence of a hypersensitivity of the heart to thyroid hormones, associated with an increased number of T3 nuclear receptor sites in lymphocytes.

Carbimazole↗
PubMed1988

Long-term follow-up of patients treated with VVI pacing and sequential pacing with special reference to VA retrograde conduction.

The aim of this prospective study is comparing long-term prognosis in patients implanted with a VVI pacemaker (group A) with those implanted with a sequential pacing device, AAI or DDD, (group B). Both groups of 45 patients each, were comparable as regards to age, sex, pacing indications, underlying heart disease, and technical conditions of implantation and were followed-up over 55 months. Atrial arrhythmias (A.A.) incidence was higher in group A: 24.4% than group B: 8.8% (P less than 0.05). Arterial embolisms (A.E.) occurred in group A patients only. Worsening or occurrence of exercise limitation was more frequent in group A: 35.6% as compared to group B: 13.3% (P less than 0.05) and deaths related to these complications, occurred in seven cases in group A versus four cases in group B. In group A, all patients who experienced a worsening or occurrence of an A.A. or an A.E., had a ventriculoatrial conduction (VAC). No statistical difference was observed in worsening or occurrence of exercise limitation between patients with VAC and those without VAC: nine (42.8%) and seven (29.2%) but they respectively experienced at least one complication in 16 cases (76.2%) and seven cases (29.2%) (P less than 0.01). In conclusion, long-term prognosis in patients implanted with VVI pacing as compared to patients implanted with sequential pacing is poorer. The presence of VAC in patients treated with permanent VVI pacing is a major factor for complications and deaths related to A.E. and cardiac failure. Thus VVI pacing should be avoided in patients with VAC.

Arrhythmias, Cardiac↗
PubMed1986

Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog.

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day. This schedule was chosen in order to measure acebutolol plasma concentrations just before ligation from 60 to 540 min after the last dose of the drug. Long term oral treatment with acebutolol protected against postischaemic ventricular fibrillation and significantly reduced the incidence of both early phase (0-10 min postocclusion) ventricular arrhythmias and ventricular fibrillation. As a result the outcome was significantly improved after 60 min of ischaemia in acebutolol compared with placebo treated animals. The results in the control animals were similar to those in the placebo treated dogs. The protective effect of long term oral treatment with acebutolol lasted for nine hours and was apparently independent of the plasma concentrations of the drug. These data show that improved outcome in this canine model is due to the prevention of ischaemia induced ventricular fibrillation by long term beta adrenoceptor blockade, which is able to overcome the effect, if any, of partial agonist activity of acebutolol. A direct myocardial anti-ischaemic effect might explain the effectiveness of long term oral treatment, which is independent of plasma concentrations of the drug.

Acebutolol↗
PubMed1986

The QT-sensitive cybernetic pacemaker: a new role for an old parameter?

A critical review of the available data on QT interval is presented to delineate techniques useful to the development of a QT-sensitive cybernetic pacemaker. The reason for the development of this unit stems from the ability of QT prolongation to predict the onset of life-threatening ventricular arrhythmias in some clinical situations; the QT interval is physiologically related to the cardiac cycle length, therefore providing adequate information to drive both ventricular and atrioventricular sequential rate-responsive pacemakers. This unit might also monitor cardiac rhythm and detect the pathophysiologic precursors of advanced grades of ventricular arrhythmias. A therapeutic role, both pharmacologic and electrical, may also be possible in the future. Integration of these concepts and cooperation between interested physicians, technicians and manufactors will be necessary to produce such a unit at a low cost-benefit ratio. The potential clinical application of this pacemaker deserves attention for the prophylaxis and treatment of sudden arrhythmic death.

Arrhythmias, Cardiac↗
PubMed1979

[Presentation of continuous electrocardiograms in compressed form. Preliminary note].

The conventional electrocardiogramme is poorly suited to the study of continuous electrocardiographical recordings. The rapid interpretation of recordings obtained by the Holter method is not compatible with the preservation of an analogous record of the whole period under study. The study of continuous electrocardiogrammes by computer uses only part of the data recorded. The technique of compression based on the principle of Contourography is a method of preserving continuous electrocardiographical records in their analogical form. This recording is a useful addition to the Holter method.

Electrocardiography↗
PubMed1978

Properties of solubilized nuclear triiodothyronine binding proteins.

Rat liver nuclear proteins bind 3,5,3'-triiodo-L-thyronine (T3) to essentially one class of sites (Ka approximately 1 X 10(10) M-1). Gel filtration and sucrose gradient centrifugation studies show a main T3 binding component with a Stokes radius of 33 A and a sedimentation coefficient of 3.5S, and variable amounts of high molecular weight binding components, most of them being reversible aggregates of the main component formed during storage. But the uniqueness of the nuclean T3 binding proteins (NTBP) cannot be ascertained from polyacrylamide gel electrophoresis data. During storage in the absence of reducing agents, NTBP aggregate and rapidly lose their ability to bind T3; T3--NTBP complexes also aggregate and progressively dissociate. This can be reversed by dithiothreitol. Bound T3 could temporarily stabilize the binding site but cannot protect NTBP against general conformational changes which follow the oxidation of their essential --SH group(s). NTBP are DNA binding proteins with probably a relative independence of their DNA and T3 binding sites: they bind T3 to the same class of high affinity sites whether complexed or not with DNA; bound T3 is not a prerequisite for DNA binding.

Animals↗