Biomedical subjects

J Bismuth

Publications and source records attributed to J Bismuth.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1990

Distribution of the MHC antigens after liver transplantation: relationship with biochemical and histological parameters.

The aim of this study was to analyse the change in tissue distribution of HLA class I and class II molecules in patients during the course of liver transplantation. Sixty-one liver biopsies were analysed in 24 patients with or without rejection (acute or chronic) episode. In 93% of cases with chronic rejection and in 48% of cases with acute rejection episodes, HLA class I antigens are expressed in the membrane and/or the cytoplasm of hepatocytes. The expression of these molecules was significantly correlated with the ASP (aspartate amino transferase), AP (alkaline phosphatase), the bile duct damage and the centrolobular lesions. In contrast, the expression of HLA class II molecules is not correlated with either the type of rejection, the biological or histological findings. A strong expression of HLA class I antigen on hepatocytes after day 60 may be one of the best signs of chronic rejection.

Graft Rejection↗

PubMed1990

Mitochondrial activity of rat kidney during ontogeny.

The development of oxidative metabolism was studied from the late fetal to adult stages in mitochondria isolated from rat kidney. We used the oxygen consumption rate, as an index of inner membrane activity and citrate synthase and fumarase activities as an index of matrix activity and cytochrome c oxidase activity as an index of the number of mitochondria. Fumarase and citrate synthase activities displayed different developmental patterns, suggesting that these Krebs cycle enzymes did not mature synchronously. In fetal mitochondria, net oxygen consumption measured in the presence of succinate or glutamate as substrate, was low; it increased during the day after birth and reached adult level between days 10 and 15. During this period, the levels of citrate synthase and cytochrome c oxidase activity did not change significantly in the isolated mitochondrial fraction. However, in fetal and adult kidney homogenates, these levels increased four-fold, suggesting a corresponding increase in the number of mitochondria. Most of these increases occurred during the 15 days after birth. These results suggest that in rat kidney, mitochondrial maturation precedes the maturation of reabsorptive ion transport and does not limit its development.

Adenosine Diphosphate↗

PubMed1989

Heterogeneous distribution of nuclear triiodothyronine receptors in liver and preadipose cells as evidenced by their reactivity to antibodies against different protein products of erb A oncogenes.

Polyclonal antibodies raised in rabbits against bacterially produced peptides in the C-terminal region of v-erb A or human c-erb A alpha oncogenes recognize the nuclear triiodothyronine (T3) receptors in the T3-sensitive Ob 17 mouse preadipocyte cell line and not in mouse or rat liver. The results confirm the existence of different T3 receptors in different tissues. The results also suggest a heterogeneous receptor distribution within the preadipose cell line, with a predominance of c-erb A alpha-type species. Antibodies raised against domain 149 227, but not against domain 245-325, impair T3 binding, suggesting a role for this domain in ligand binding.

Adipose Tissue↗

PubMed1988

Effects of birth on energy metabolism in the rat kidney.

The oxygen-consumption rates and the activities of fumarase and beta-hydroxyacyl-CoA dehydrogenase were compared in mitochondria isolated from fetal- and neonatal-rat kidney. Whole-organ ATP, phosphocreatine and creatine contents were determined in parallel. Kidney mitochondrial respiratory rates in the presence of succinate, glutamate/malate and palmitoyl-L-carnitine increased between 21 days post coitum and 1 day post partum, together with activities of oxidative enzymes. However, this postnatal maturation of oxidative metabolism was not yet initiated in mitochondria isolated from kidney 1 h post partum. An increase in ATP and phosphocreatine was observed immediately after delivery; newborn-rat kidney ATP content then remained high, whereas phosphocreatine reserves decreased considerably between 6 h and 1 day post partum. It is concluded that the increase in high-energy phosphate compounds observed at birth is not initially related to an activation of oxidative phosphorylation, and probably involves a transient stimulation of anaerobic glycolysis, while a progressive mitochondrial maturation takes place in the rat kidney during the first day of newborn life.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1988

Nuclear T3 receptor: depletion by tunicamycin despite the absence of N-linked glycan units in a murine preadipocyte cell line and rat liver.

In experiments designed to evaluate the possible presence of N-glycan units in the nuclear T3 receptor, tunicamycin markedly depleted the nuclear T3 receptor sites when added to the culture medium of the T3 responsive ob 17 preadipocyte cell line under conditions which almost totally abolished protein N-glycosylation without significant alteration of protein synthesis. The affinity for T3 was unchanged. However, no significant interaction could be detected between the T3 receptor solubilized from the ob 17 cells, or from rat liver, and several insolubilized lectins of different specificities. Furthermore, treatment of the cells with swainsonine, a Golgi mannosidase II inhibitor, did not lead to any significant interaction of the receptor with concanavalin A as it would have occurred if the receptor had contained complex glycan units unrecognized by this lectin. These results are strong arguments against the presence of N-glycosidic moieties in the nuclear T3 receptor from mouse adipose cells and rat liver. The receptor sites depletion after tunicamycin treatment may most probably reflect an indirect effect through other glycoproteins which could be on the one hand required for either receptor stabilization or localization in the chromatin, or on the other hand involved in receptor level regulation.

Adipose Tissue↗

PubMed1987

Role of catecholamines in the control of newborn kidney adenine nucleotide content.

During the 1st h of extrauterine life, the adenine nucleotide content of the rat kidney is modified: the ATP level increases (+30%) while ADP and AMP are lowered (-30 and -50%, respectively). This leads to a high value of energy charge in the newborn kidney (0.89 vs. 0.80 in the fetus). It was possible to obtain in utero a similar modification of ATP, ADP, AMP concentrations by injections to the fetuses of cAMP, dibutyryl cAMP, or isoprenaline. Conversely, the postnatal changes in adenine nucleotide content could be prevented by administration to the fetus, just before birth, of beta- or beta 1-adrenoreceptor antagonists. Therefore the rise of kidney energy charge following parturition appears to be under hormonal control. Glucagon had no effect on kidney adenine nucleotide content. It is strongly suggested that the catecholamines released at the time of parturition are the triggering factor of this evolution.

Adenine Nucleotides↗

PubMed1987

[Mitochondrial oxidative phosphorylation in the rat kidney during the perinatal period].

Oxidative metabolism in the developing rat kidney has been studied on isolated mitochondria. An increase of about 50% in state 3 respiration has been observed at birth, using succinate, glutamate, or palmitoyl-L-carnitine as a substrate. The rate of respiration in the presence of 2,4-dinitrophenol was found identical to state 3 respiration in all cases. Cytochrome oxidase activity did not change between the fetal and newborn stages. The increase of mitochondrial respiration revealed here, which is not linked to a modification of the respiratory chain, could be involved in the rise of kidney ATP level and energy charge observed at birth.

Aging↗

PubMed1986

Triiodothyronine (T3)-induced down-regulation of the nuclear T3 receptor in mouse preadipocyte cell lines.

As previously reported, preadipocytes cloned from the epididymal fat of lean or genetically obese mice (HGFu and ob 17, respectively) contain the nuclear T3 receptor. The number of receptor sites was similar in confluent cells of both lines and approximately doubled during adipocyte differentiation. T3 added to the culture medium increased triacylglycerol synthesis. T3 also increased fatty acid synthase specific activity, relative synthesis rate, and relative mRNA content (1.5- to 2.5-fold). Optimal responses were obtained at 1.5 nM. This study shows that under the same culture conditions in both cell lines, 1.5 nM T3 decreased the receptor concentration with no significant change in the affinity for T3. The receptor depletion was time dependent, rapid, stable in the presence of T3, and reversible in less than 24 h after its withdrawal. Receptor depletion was also dependent on T3 concentration and close to maximum at 1.5 nM T3 [45.1 +/- 2.7% (+/- SE) of the data values without T3; n = 14]. A linear relationship was observed between receptor occupancy by T3 and receptor loss. T4 and triiodothyroacetic acid also decreased the T3 receptor content, as expected from their own affinity for the receptor. These last two observations suggest that the receptor reduction is related to its occupancy by T3. The reported results, also observed in several other cell types, indicate that down-regulation of the nuclear T3 receptor by thyroid hormones is probably a generalized event in T3 target cells at least in vitro. Interpretation of its significance in preadipocyte cell lines requires further studies of rapid nuclear events following T3 receptor occupancy.

Adipose Tissue↗

PubMed1986

Perinatal changes in adenine nucleotide content of developing rat kidney.

Adenine nucleotides have been measured in fetal and newborn kidneys of rat using the luciferine-luciferase method. In fetuses, between days 18 and 21 of gestation there is a drop of the relative amount of ATP in the renal nucleotide pool. Consequently, the kidneys of 21 days-old fetuses have lowered ATP/ADP ratio (3.6) and energy charge (0.80) compared with values found on day 18 (6.9 and 0.91, respectively); this relative energy deficit is heightened in progesterone induced postmaturity. One hour after delivery whether the gestational stage is 21, 22 or 23 days, there is a rise in ATP and a decrease in AMP content which restore a high energy level in kidney of the newborn and a 30% increase in the total adenine nucleotide pool.

Adenine Nucleotides↗

PubMed1985

Triiodothyronine nuclear receptor and the role of non-histone protein factors in in vitro triiodothyronine binding.

The rat liver triiodothyronine (T3) nuclear receptor rapidly looses, after a partial purification from the nuclear extract, its ability to bind T3. We previously reported that histones, in the presence of DNA, could protect against inactivation enhancing the T3 binding site concentration and maintaining the high affinity for T3. A nuclear fraction discarded during the receptor purification (fraction A) was also found able to restore T3 binding and was analyzed. As histones + DNA, fraction A stabilized the T3 binding site from irreversible inactivation during incubation with T3, increasing its concentration while keeping the same high affinity for T3. It was active even at relatively high receptor concentration, appeared slightly more active than histones (+ DNA) in the same protein concentration range (up to 50-fold increment of T3 binding at the optimal concentration of 25 micrograms/ml) and was unaffected or slightly inhibited by DNA. Other proteins (ovalbumin, soybean trypsin inhibitor, RNAase) and rat liver cytosol were several times less effective, suggesting a major role of some nuclear constituents. The active factors in fraction A essentially belong to non-histone nuclear proteins. Fraction A was found heterogeneous regarding the molecular size and pHi of the active factors, the existence of subfractions more active on a protein concentration basis being suggested but not yet clearly evidenced. Efficient in vitro T3 binding to the isolated T3 nuclear receptor thus depends on the presence of several different nuclear constituents, histones + DNA or some non-histone proteins. Whether interactions with these constituents could modulate T3 binding within the nucleus remains to be elucidated.

Animals↗

PubMed1984

[Changes in the nuclear triiodothyronine receptor during the differentiation of preadipocytic cell lines of mice].

During the differentiation process of ob 17 preadipocytes in the presence of insulin, a progressive increase in the nuclear T3 receptor concentration per cell (1.5 to 3 fold) was observed. This increase was not found related to the addition of insulin to the culture medium and was concomitant to the expression of several phenotypes of the mature adipocyte. Triiodothyronine (T3) added to the culture medium of these cells increases the lipogenic pathway and several enzymes involved in fatty acid synthesis and esterification. After T3 addition at the same optimal physiologic concentration of 1.5 nM, the cellular concentration of its nuclear receptor was clearly reduced, without any significant alteration in the apparent affinity constant. A similar behavior was observed in 3T3-L1 preadipocytes. The molecular mechanism of action of the T3 nuclear receptor within the chromatin is not known. The biological relevance of its depletion by T3 itself remains to be determined.

Adipose Tissue↗

PubMed1983

Triiodothyronine nuclear receptor. Role of histones and DNA in hormone binding.

The triiodothyronine (T3) nuclear receptor was previously shown to lose rapidly its high affinity hormone-binding property after a partial purification from the nuclear extract. It was then found that histones + DNA added to the incubation medium with labeled T3 could restore, at least in part, the high affinity T3 binding. We now demonstrate that DNA alone increases the high affinity T3 binding site concentration moderately, and only at low ionic strength where it can bind to the receptor. Total histones and all histone fractions studied (total core histones, F2a, H2B, H3, H4, H1) specifically increase, at low concentrations, the level of T3 binding; but higher concentrations of some individualized histones, particularly arginine-rich histones, have an inhibitory effect. DNA, or several other polynucleotides, in the presence of histones increase the stimulating histone effect and reverse the inhibitory effect into a true activation. Histones increase the number of T3 binding sites but decrease the affinity for T3; addition of DNA restores the high affinity for T3 and stabilizes the T3-receptor complexes. Thus, some of the histone molecules could play a role in the maintenance of the T3 binding site, but multiple interactions between histones or with DNA seem necessary to impair the negative effect exerted by other parts of the histone molecules. Whether these positive and negative effects of histones on the T3 binding site are of biological relevance in the regulation of T3 binding to its receptor remains to be determined.

Animals↗

PubMed1983

The effect of triiodothyronine on fatty acid synthetase activity and content in differentiating ob17 preadipocytes.

The effect of triiodothyronine on the activity and amount of the key lipogenic enzyme fatty acid synthetase was studied in differentiating preadipocyte cells (ob17) isolated from ob/ob mouse epididymal fat pad. In the presence of physiological concentrations of insulin, the acquisition of adipose morphology was accompanied by a parallel increase (10--15-fold) in synthetase specific activity and radioimmunoassayable amount relative to soluble cellular proteins. Inclusion of T3 at confluence significantly enhanced synthetase activity and content, with a maximum of 1.5--2-fold above controls at the physiological 1.5 nM concentration, whether insulin is present or not. During adipose conversion, T3 increased the development of enzyme activity and after a longer lag period, the accumulation of the synthetase. Our results suggest that the stimulating effect of T3 upon synthetase activity could involve as a first step the activation of preexisting inactive synthetase molecules and as a second one an increased accumulation of activable synthetase. After longer culture periods, inactive radioimmunoassayable synthetase accumulated.

Adipose Tissue↗

PubMed1983