Sexual transmission of hepatitis C virus.
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Adult↗
Biomedical subjects
R Vranckx
Publications and source records attributed to R Vranckx.
A senescence up-regulated protein: the rat thyroxine-binding globulin (TBG).
Thyroxine-binding globulin (TBG), the major carrier of thyroid hormones in human serum, was thought to be absent in most species, including rodents. We demonstrated recently that in fact the rat possesses a TBG gene, virtually non-expressed in young adults, but actively transcribed during post-natal development. We now find that the TBG gene is also increasingly re-expressed during senescence. Evidence is presented suggesting that physiologically decreased thyroid hormone levels, characteristic of neonates and of ageing rats, might constitute a common factor inducing up-regulation of TBG in both developmental and ageing processes. Rat TBG is to our knowledge the first biochemical 'positive' (i.e. increasing) marker of non-pathological senescence, expressed at both biosynthetic and bloodstream levels.
Aging↗
Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse.
We confirm our finding of a major development-regulated thyroxine-binding globulin (TBG) in the serum of the euthyroid mouse and investigate a number of its binding, structural and regulatory properties. Between 16 days foetal and 60 days postnatal life, the thyroxine (T4)- and tri-iodothyronine (T3)-binding activities of the sera show a striking ontogenic pattern: the binding is 2-3 times higher in foetuses than in mothers, then further increases after birth, reaching between 3 and 5 days maximum values which are 7-8 times higher than the adult ones. This pattern is not correlated with the ontogenesis of the acknowledged specific (transthyretin, TTR) and non-specific (albumin, alpha 1-foetoprotein) thyroid-hormone carriers of the mouse sera. PAGE studies demonstrate that the protein responsible for the elevated binding of the perinatal period is an alpha 1-globulin, with a migration similar to that of human and rat TBGs. Scatchard analysis is consistent with the notions that the T4-binding sites of TBG have high association constants, about two orders of magnitude above the T4 sites of TTR (10(9) M-1 as against 10(7) M-1) and low capacities (37 and 4 nmol/g of serum proteins in pups and adults respectively). Isoelectric focusing (i.e.f.) demonstrates that mouse TBG is a microheterogeneous protein separable, as a function of the pH gradient, in up to 10-12 isoforms, Marked shifts of the relative abundance of isoforms in the course of development are evidenced. The modulation of the TBG binding activity by non-esterified fatty acids (NEFA) and the control of its synthesis by the thyroid status are also reported. Mono- and poly-unsaturated NEFAs are strong inhibitors of the TBG, although they affect TTR less readily. On the other hand, the biosynthesis and/or secretion of TBG, but not of TTR, is under thyroid-hormone control, experimental hypothyroidism inducing a marked increase of the serum TBG. The TBG of mouse behaves as a highly significant parameter of development, pointing to a likely important function of the protein in the process of maturation. Our finding of major TBGs in both euthyroid rats and mice suggests that TBG is more widely spread than was thought until now, but difficult to detect in certain species outside definite maturation stages.
Aging↗
Hepatitis C in institutionalized children.
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Child↗
The hepatic biosynthesis of rat thyroxine binding globulin (TBG): demonstration, ontogenesis, and up-regulation in experimental hypothyroidism.
Using a human thyroxine binding globulin (TBG) cDNA probe, we demonstrate that rat liver contains two TBG mRNA species of different length, consisting of about 1.8 Kb and 2.4 Kb respectively. Slot blot analysis of the hepatic mRNAs from rats of different age reveals a fair correlation between the developmental trend of the messengers and that of the TBG circulating levels. Finally Northern blot and slot studies demonstrate that the increase of serum TBG induced in adults by thyroidectomy actually reflects an enhanced hepatic biosynthesis of the protein.
Animals↗
Evaluation of a line immunoassay for the differential detection of antibodies to human immunodeficiency virus.
A newly introduced single strip line immunoassay was evaluated as a possible alternative to Western blot for the differential detection of antibodies to multiple HIV-1 and HIV-2 antigens in human serum. In a panel of 153 sera found to be positive twice in currently used screening tests, the line immunoassay and the Western blot detected 44 true positive results. Using Western blot as reference method, the line immunoassay gave 100% specificity and sensitivity. These results suggest that the line immunoassay may be a viable alternative to Western blot.
AIDS Serodiagnosis↗
Immunogenicity of a recombinant DNA hepatitis B vaccine in institutionalized patients with Down's syndrome.
Residents of institutions for the mentally handicapped, especially Down's syndrome (DS) patients, are at increased risk for exposure to hepatitis B virus (HBV). Indeed, during a serological survey of 770 mentally retarded residents in institutions in Antwerp in 1985, 32.6% of the 92 DS patients screened were HBsAg positive, compared with 7.2% of the 678 other mentally retarded (OMR) patients (p less than 0.001). Seronegative mentally handicapped individuals (275 in number including 18 DS patients) from three institutions were vaccinated with 20 micrograms of a recombinant yeast-derived hepatitis B vaccine (YDV) according to a 0, 1, 6 month schedule. Serum samples were tested at months 1, 2, 7, 12 and 24 for HBV markers by radioimmunoassay. One month after the third vaccine dose, 81.3 and 97.7% of DS and OMR patients had seroconverted, respectively, with GMTs of 516.3 and 1078.7 mIU ml-1. Two years after the start of the vaccination course, 66.7 and 96% of subjects in the two groups still had protective antibody levels (greater than or equal to 10 mIU ml-1), although GMTs had decreased to 40.1 and 166.3 mIU ml-1 in the two groups, respectively. Only one of the 18 DS patients had transient asymptomatic anti-HBc infection at month 2, no subject followed up being infected after the full vaccination course. Thus, the institutionally mentally handicapped, including DS patients are capable of responding adequately to YDV.
Adolescent↗
A seroepidemiological survey of HTLV-I/HTLV-II in selected Belgian populations.
A preliminary survey of the prevalence of HTLV-I antibody during 1987 and 1988 in Belgium revealed no positive results among selected blood donors who sided for some length of time in areas where HTLV-I/HTLV-II is endemic (n = 270), in development-aid workers (n = 145), or in missionaries (n = 35) serving in developing countries. Among foreign groups, African students (n = 212), and political refugees (n = 311), HTLV-I/HTLV-II antibodies were detected and confirmed in 3 cases. Limited data from 1987 and 1988 suggest that HTLV-I/HTLV-II poses no major public health problem in Belgium.
Adult↗
Effect of adrenalectomy at different pregnancy stages on maternal and fetal serum corticosteroid binding globulin and corticosterone in the rat.
The response of pregnant rat corticosteroid binding globulin to maternal adrenalectomy was studied as a function of the stage of pregnancy. Non-pregnant or pregnant rats were deprived of their adrenal glands during 4 days. In non-pregnant animals, adrenalectomy led to undetectable corticosterone levels and to the doubling of corticosteroid binding globulin. In pregnant rats adrenalectomized at 12 days and studied at 16 days, the serum corticosterone was likewise undetectable and the corticosteroid binding globulin was doubled as compared with pregnant rats of the corresponding age. In contrast, adrenalectomy from day 14 to 18 or from day 16 to 20 did not deplete the maternal serum corticosterone and the corticosteroid binding globulin remained unchanged. Under these conditions neither fetal corticosteroid binding globulin nor fetal corticosterone were modified. However, when the pregnant rats adrenalectomized from day 16 to 20 also received an injection of 30 mg of metyrapone on days 19 and 20 in order to inhibit fetal adrenal secretion, the maternal response was again a depletion of serum corticosterone together with an increase in corticosteroid binding globulin. Under these conditions, the fetus also reacted by a fall of corticosterone and a rise of corticosteroid binding globulin. Our results suggest that the maternal response of corticosteroid binding globulin to adrenalectomy depends on the pregnancy stage inasmuch as it may be influenced by a supply of corticosterone from the fetus during late pregnancy. Moreover, they show that in this late period, fetal corticosteroid binding globulin is regulated independently.
Adrenal Glands↗
Immunological quantitation of rat and mouse thyroxine-binding globulins. Ontogenesis and sex-dependence of the circulating levels of the thyroxine-binding globulins.
We describe the preparation of monospecific antisera against a thyroxine-binding globulin partially purified from immature rat sera by affinity chromatography on thyroxine-Sepharose. The antisera are used for the rocket immunoelectrophoresis assay of rat thyroxine-binding globulin and also, owing to their partial cross-reactivity with mouse thyroxine-binding globulin, for the quantitation of this serum binding protein in the mouse. The thyroxine-binding globulin is measured in developing rats and in sexually mature male and female rats and mice. The results of the ontogenetic study confirm the postnatal surge of serum thyroxine-binding globulin levels, formerly demonstrated with binding techniques. They allow further to define the correlations, dependent on age, of the immunoquantitated thyroxine-binding globulin and transthyretin levels with the abilities of the sera to bind thyroxine. In sexually mature rats and mice we demonstrate an opposite sex-dependence of thyroxine-binding globulin levels, characterized by increased levels of the protein in the female rats versus increased levels of the protein in the male mice. This is the first report of immunological quantitation of rat and mouse thyroxine-binding globulins.
Aging↗
Thyroxine-binding globulin and thyroxine-binding prealbumin in hypothyroid and hyperthyroid developing rats.
We present evidence based on equilibrium and non-equilibrium binding studies, as well as on immunological techniques, that of the two rat specific thyroid-hormone-binding proteins, i.e., thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA), TBG but not TBPA is regulated by the thyroid hormones (TH). Hypothyroidism, induced from the day of birth by daily treatment with propylthiouracil (PTU-rats), leads to dramatic and sustained increases of the TH-binding abilities of the sera measured at equilibrium, whereas hyperthyroidism, induced by treatment with thyroxine (T4-rats), leads to the decrease of these abilities. Polyacrylamide gel electrophoresis and isoelectrofocalisation of radioiodinated T4-labelled sera, together with immunoassay of TBPA, demonstrate that both effects are due to TBG, the levels of which rise in PTU-rats and decline in T4-rats, while TBPA levels do not respond to either depletion or excess of the thyroid hormones. TBG rather than TBPA appears as the key thyroid-hormone-binding protein of the rat, inasmuch as it alone expresses a regulatory function of the thyroid hormones at protein synthesis level.
Aging↗
Protective efficacy of a recombinant deoxyribonucleic acid hepatitis B vaccine in institutionalized mentally handicapped clients.
Mentally handicapped clients in institutions are at high risk for hepatitis B virus (HBV) infection. In 1985, 770 mentally handicapped residents from four institutions in the Antwerp area were screened for HBV markers. The prevalence of hepatitis B surface antigen was 10.3 percent (range, 6.1 to 15.2 percent); 42.3 percent (range, 11.5 to 60.1 percent) had antibodies to hepatitis B surface antigen and the hepatitis B core antigen. In 1986, 275 seronegative mentally handicapped residents were vaccinated intramuscularly in the deltoid region with 20 micrograms (1.0 ml) of a recombinant deoxyribonucleic acid yeast-derived hepatitis B vaccine (Engerix-B, SmithKline Biologicals, Rixensart, Belgium) on a zero-, one-, six-month schedule. Serum samples were collected at Months 1, 2, 7, 12, and 24 and were tested for HBV markers by radioimmunoassay. The seroconversion rates for hepatitis B surface antigen antibodies were 39 percent at Month 1 (geometric mean concentration, 6.4 IU/liter), 82 percent at Month 2 (geometric mean concentration, 23.4 IU/liter), 97 percent at Month 7 (geometric mean concentration, 1,034 IU/liter), and 96 percent at Month 12 (geometric mean concentration, 269 IU/liter). Among the 214 residents evaluated at Month 12, 69 percent had hepatitis B surface antigen antibody levels greater than 100 IU/liter (geometric mean concentration, 603 IU/liter). No significant adverse reactions were observed. Within the first seven months of observation, HBV infection was detected in eight of 271 subjects (estimated annual incidence of 5 percent). During this period, none of the clients developed clinical hepatitis or showed biochemical evidence of liver damage. Between eight and 24 months, no additional HBV infections were detected. These data can be compared with an annual incidence of HBV infection of 8.7 percent in a historical cohort of mentally handicapped residents in one of the four institutions.
Adolescent↗
Conformational changes in rodent and human alpha-fetoprotein: influence of fatty acids.
Binding, spectral and immunological studies were performed to demonstrate the conformational changes in rodent and human alpha-fetoprotein (AFP) induced by a free fatty acid environment. Scatchard analysis of estradiol (E2) binding to purified rat AFP indicated that unsaturated fatty acids changed the number of binding E2 sites and the apparent E2 equilibrium dissociation constant which varied non-linearly with docosahexaenoic acid concentration. UV spectral analysis of rodent and human AFPs showed that the absorbance minimum of AFP incubated with unsaturated fatty acid (L-AFP) was red-shifted, broadened and less pronounced than that of purified native AFP (N-AFP). Immunochemical studies with specific polyclonal antibodies to purified rodent and human AFPs (N-AFP antibodies) showed that these proteins lost immunoreactivity after incubation with unsaturated fatty acid. N-AFP antibodies recognized fewer epitopes on L-AFP than on N-AFP, whatever the species. Specific anti-rat L-AFP antibodies were used to demonstrate specific epitopes on rat L-AFP. Rat L-AFP antibodies did not recognize rat N-AFP. Saturated fatty acids were without effect on the binding, spectral and immunological properties of rodent and human AFPs. RIA or ELISA values for human AFP from fetal serum, hepatoma serum, and cord serum, were reduced 80, 50 and 5%, respectively, by unsaturated fatty acids. This decrease correlated with the relative percentage of polyunsaturated fatty acid in each biological fluid. Such results indicate that an unsaturated fatty acid environment induces conformational changes in AFP which may modulate the endocrine and immune functions of this protein.
Animals↗
Binding activities of thyroxine binding globulin versus thyroxine binding prealbumin in rat sera: differential modulation by thyroid hormone ligands, oleic acid and pharmacological drugs.
We use gel equilibration and electrophoretic techniques to compare the binding properties of thyroxine binding globulin and thyroxine binding prealbumin in rat sera. The evidence indicates that TBG bears the serum lowest capacity highest affinity sites for thyroxine (T4) and triiodothyronine (T3) (Ka1 greater than or equal to 10(9) M-1) as well as weaker saturable T3 sites (Ka2 approximately 10(8) M-1). TBPA bears for T4 only Ka2 approximately 10(8) M-1 sites and for T3 only Ka approximately 10(6) M-1 sites. Consistent with these parameters are the specific responses of TBG and TBPA binding activities to varying serum concentrations of T4, T3, oleic acid, the drugs diphenylhydantoin or salicylate. The primary attack of these compounds is aimed at TBG. Small T4, oleate or DPH doses chase the TBG-bound T4 to TBPA, high doses of T4 or oleate but not of DPH inhibiting the T4 binding to both proteins. In the T3-serum interactions, all tested compounds displace the TBG-bound hormone without chasing it to TBPA. The high reactivity of TBG sites designates the protein as crucially involved in modulating the free vs bound serum levels of T4 and T3 against physiological or pathological variations of binding competitors.
Animals↗
The microheterogeneity of rat TBG.
Isoelectric focusing (IEF) of native sera from immature or adult rats and of purified or partially purified rat serum thyroid hormone-binding proteins, demonstrates that rat TBG is a microheterogeneous protein. Autoradiography and radioactivity scans of the IEF plates show that it consists of at least four main isoforms, with bands at pH 4.35, 4.45, 4.5 and 4.55. This pattern is remarkably similar to that reported for human TBG. This is the first demonstration of the polymorphism of this recently discovered major binding protein of the rat.
Aging↗
Inflammatory competence of fetal rat: acute-phase plasma protein response of the fetus treated by turpentine in utero.
Using crossed immunoelectrophoresis, immunoelectrodiffusion, autoradiography, and equilibrium binding techniques, we demonstrate that the rat fetus, directly challenged in utero at 18 days by a single subcutaneous turpentine injection, presents a complex acute-phase plasma inflammatory response. A number of fetal serum proteins, 48 h after the injection, increase in concentration by factors of about 2-5. These positive acute-phase reactants (APR) are alpha 1-acute-phase globulin (alpha 1-AP), alpha 2-macroglobulin (alpha 2-M), alpha 1-acid glycoprotein (alpha 1-AG), haptoglobin (Hp), and hemopexin (Hpx). A number of proteins decrease, behaving like negative APRs. These are albumin, alpha 1-fetoprotein (AFP), transferrin, GHR-P63, thyroxine-binding prealbumin (TBPA), and transcortin (CBG). The marked fall in concentration of two of the high-affinity hormone-binding proteins of the fetal rat, i.e., the estrophilic AFP and TBPA, induce significant decreases (by 25-40%) of the estrogen- and thyroxine-binding abilities of the fetal serum. While the plasma inflammatory response of the fetus is qualitatively similar to that of the adult, the fetal reactions are, as a rule, quantitatively weaker. The characteristics of the plasma inflammatory response of the fetus are discussed in relation to the highly dynamic state of its development.
Acute-Phase Proteins↗
[A thyroxine-binding globulin of major biological significance in the serum of mice: demonstration and ontogenesis].
We demonstrate in the mouse serum a hitherto unrecognized major thyroxine binding globulin (TBG), analogous to human TBG or to the recently discovered rat TBG. Our demonstration is based on equilibrium dialysis, electrophoresis, immunoelectrodiffusion and autoradiography techniques. Mouse TBG displays a remarkable ontogenic pattern, with 2-3 times higher activity in foetal than in maternal serum, and a further dramatic increase after birth. Between 1 and 5 days, the T4 binding to serum reaches peak levels 7-10 times more elevated than those measured in normal or pregnant adults. We also present for the first time the ontogenesis of the thyroxine binding prealbumin (TBPA), considered until now as the only specific T4 carrier of the murine species. We show that throughout development it is the TBG, not the TBPA, which crucially governs the level of the T4-serum interactions.
Aging↗
[Political refugees: an important risk group for AIDS and hepatitis B?].
This prospective study shows that the prevalence of HIV and HBV in political refugees who arrived in Belgium between November 1988 and January 1989 was as follows: --Africans (mostly coming from Central Africa) 3.7% positive for HIV antibodies; 12.4% positive for HBsAg. --Asians (mostly coming from Middle and Southeast Asia) 0.2% positive for HIV antibodies; 8.4% positive for HBsAg. --Europeans (mostly coming from Southeast Europe) 0% positive for HIV antibodies; 14.8% positive for HBsAg. These figures indicate that all political refugees arriving in Belgium belong to a high-risk group for HBV infections and that, in addition, Africans also are in the high-risk group for HIV infection. It seems appropriate to test all persons wishing to take up residence in Belgium for the presence of HIV, HBV and HTLV-I, not so much because these viral infections are less frequent in that country but rather to offer the carriers of these infections adequate counselling.
Africa↗