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Biomedical subjects

P De Nayer

Publications and source records attributed to P De Nayer.

At least 19 recordsLinked to original sources
PubMed1992

The thyroid hormone receptors: molecular basis of thyroid hormone resistance.

Major progress has been achieved in the mechanism of action of thyroid hormones thanks to the identification of the T3 receptor as the product of the proto-oncogene c-erbA. Recognition of subsets of receptors with and without T3-binding properties and of the interaction of different receptors with each other leads to new insights in cell regulation and development. In thyroid hormone resistance, distinct mutations in the T3-binding domain of thyroid hormone receptor (TR)beta have been identified in unrelated families. No correlation between the type of mutation and tissue resistance has been established. Mutant TRs bind to thyroid hormone response elements (TREs) on both negative or positive T3-controlled genes. Subjects with heterozygous TR beta gene deletion are not affected, supporting the hypothesis that mutant TRs act through a dominant negative effect. In generalized thyroid hormone resistance, mutated TR beta may interfere through competition for TREs and/or formation of inactive dimers. Finally, deficiency in T3 receptor auxiliary protein or other accessory proteins or competition between mutant and normal TRs for these factors is not excluded.

Binding Sites↗
PubMed1992

Partial reversibility during late postpartum of thyroid abnormalities associated with pregnancy.

The aim of the present work was to assess during late postpartum the reversibility of thyroidal alterations associated with pregnancy. Thyroid function was reinvestigated 6 months after delivery in 100 randomly selected healthy women and thyroid volume was reevaluated 12 months after delivery in 10 other selected women. The subjects had previously been carefully followed during gestation as they were included in a prospective cohort investigation of the regulation of the thyroid during pregnancy, in an area with a limited dietary iodine intake (less than 100 micrograms/day in 85% of the women). Six months after delivery, an overall normalization of thyroid function was observed. However, an increase in the T3/T4 ratio, which was present in half the cases at delivery, was still evident 6 months postpartum, suggesting the persistence of relative iodine deficiency, probably prolonged in some women through breast-feeding. Furthermore, serum thyroglobulin levels, which were increased in half the women at delivery, remained abnormally high in 40% of them 6 months later. Twelve months after delivery thyroid volume, which had increased in average by 54% during pregnancy, had not reverted to the values found during early gestation. Moreover a goiter was still evident in 2/4 cases in whom it had developed during pregnancy. In conclusion, the present study indicates that pregnancy may constitute a prolonged stimulus for the thyroid and shows for the first time that the alterations associated with gestation are not limited to the period of pregnancy, being only partially reversible during late postpartum. In conditions with a limited iodine intake, pregnancy constitutes a risk for the maternal thyroid: goitrogenesis does occur and may be maintained after delivery. The glandular stress of pregnancy may therefore provide a clue to understanding the high prevalence of thyroid disorders in women. The present study provides additional arguments to suggest that iodine supply be increased during pregnancy but also after parturition, in particular in breast-feeding mothers.

Cohort Studies↗
PubMed1992

No association between Alport's syndrome and antithyroid antibodies.

The presence of circulating antithyroid antibodies in a small number of patients with Alport's syndrome has led some to suggest that the two abnormalities are associated. If confirmed, such an association could have important diagnostic as well as pathophysiological implications. Using sensitive methods, we assessed the prevalence of antithyroid antibodies in 40 patients with Alport's syndrome from 28 families. Antithyroglobulin antibodies were absent in all patients. Antimicrosomal and antithyroperoxidase antibodies were absent in all but one patient. Three patients with Alport's syndrome from the latter family were negative for antithyroid antibodies. In this large number of patients we found no association between Alport's syndrome and antithyroid antibodies. Screening for the presence of such antibodies in patients with Alport's syndrome is thus not warranted. The previously reported coexistence of the two disorders might be fortuitous.

Adult↗
PubMed1992

[Aseptic necrosis of the femoral head following renal transplantation: assessment of a 25-year experience].

From June 1963 to December 1988 aseptic necrosis of the femoral head has been treated surgically in 84 renal transplant recipients (150 surgical procedures). The long-term results of drilling of the neck and head of the femur (16), cup arthroplasty (32), cemented cup (1) and hemiarthroplasty (8) were unsatisfactory, as 23 of these 57 hips underwent a secondary procedure. Total hip arthroplasty progressively became the standard procedure for treatment of hip disease in transplanted patients. Since 1971, 63 renal transplant recipients underwent 92 cemented total hip replacement (THR) as a primary (73), secondary (16) or third (3) surgical procedure for severely symptomatic femoral head necrosis. Hospital stay averaged 22 days, and follow-up averaged 53 months. Two deaths related to the surgical procedure occurred in the first 4 years of our experience (one major local sepsis, one pulmonary infection). Other postoperative complications were urinary tract infection (12), pulmonary infection 1, transient sciatic nerve irritation (3), wound hematoma (6), reversible deterioration of renal function (3) and rejection of the graft (2). Thromboembolic complications did not occur. All operated hips showed a marked symptomatic improvement. Loosening of one or both components was definite in one, probable in two and possible in three of the 33 hips followed up more than 5 years. Other late complications included dislocation (6), painful class III heterotopic ossification (4), recurrence of previous sepsis (1) and late hematogenous sepsis. Late hip revision was required in 5 cases (recurrent dislocation, 1, ossification, 2, sepsis, 2). Two renal complications (one graft infarction and one reversible acute tubular necrosis) occurred after these revisions. The functional results of THR compare favourably with the results of other surgical procedures used in our early experience. We conclude that THR has become the treatment of choice for symptomatic established osteonecrosis of the femoral head in renal transplant patients. A relatively high rate of early and late complications is nevertheless to be expected.

Adolescent↗
PubMed1991

Immunoturbidimetric assay of beta 2 microglobulin using latex particles in microplates.

A latex particle immunoturbidimetric assay in microplates has been developed for the quantitation of beta 2 microglobulin. The assay which involves three pipetting steps and one incubation, has a clinically useful range of 0.4-16 mg/l. A comparison of the method with a commercial radioimmunoassay in the analysis of 125 sera revealed a high degree of correlation. Although the assay was performed manually, it showed considerable potential for full automation.

Agglutination Tests↗
PubMed1991

Thyroid hormone receptors in brain and liver during ageing.

The binding properties--binding capacity (MBC) and affinity (Ka)--of T3 nuclear receptors were analyzed in cortex, cerebellum and liver of rats aged 3, 6, 12 and 24 months. A slight but not significant decrease of Ka was observed in different tissues of normal rats. In hypothyroid animals the Ka in cortex at 24 months was significantly lower than at 3 months. During ageing the MBC of brain receptors decreased whereas hepatic receptors were not altered. Hypothyroidism did not further affect the MBC of the receptors. The data indicate that during ageing the T3 nuclear receptors behave differently in brain and liver. The difference in MBC suggests selectivity in organ sensitivity to thyroid hormones.

Aging↗
PubMed1991

Measurement of beta 2-microglobulin in serum by a particle-enhanced nephelometric immunoassay.

A particle-enhanced immunoassay of beta 2-microglobulin in serum is described. It is based on the agglutination of complexes formed between the serum beta 2-microglobulin and latex particles coated with F(ab')2 fragments of polyclonal anti-beta 2-microglobulin antibodies. The analytical range of the method is 0.50 to 16 mg/l; it can be extended by appropriate dilution to 0.12 to 80 mg/l with good precision (CV less than 5% over the whole range). The accuracy and the precision are confirmed by a good correlation with radioimmunoassay (n = 123, r = 0.993). No error due to antigen excess was observed, even up to 292 mg/l. The main advantages of the method are its simplicity, its low cost per test and its high sensitivity (final dilution of the sample at 1/1200) with no known interference. The calibration curve is stable for at least 2 weeks.

Humans↗
PubMed1991

Osteochondral allografts in arm and forearm surgery.

Osteochondral allografting can restore the skeletal continuity anatomically after a limb salvage procedure. Evaluation of the clinical function indicates that a good result can be anticipated. Fracture was the most frequent complication, and the fixation technique we used initially predisposed the problem. The major advantage of allograft is the possibility of reinsertion of soft tissue to help stabilize the new joint. In addition, any part of the limb can potentially be reconstructed with an allograft.

Adolescent↗
PubMed1990

Amiodarone-induced thyrotoxicosis suggestive of thyroid damage.

Amiodarone-induced thyrotoxicosis (AIT) is generally believed to result from increased hormonal synthesis related to the iodine overload. Thyroid damage has recently been incriminated as a pathophysiological mechanism. We report 3 cases of AIT associated with clinical and/or biochemical features consistent with thyroid damage. This hypothesis was supported by a painful thyroid (case 1), transient high serum Tg (case 2), a transient (case 2) or persistent (case 3) hypothyroid phase and an undetectable technetium thyroid uptake during the hypothyroid period (case 3). These clinical observations support the previous histological data indicating that thyroid follicular disruption might contribute to the pathogenesis of AIT.

Adult↗
PubMed1990

Elevation of serum thyroxine-binding globulin (but not of cortisol-binding globulin and sex hormone-binding globulin) associated with the progression of human immunodeficiency virus infection.

PURPOSE: In order to assess the relation of thyroid function tests to human immunodeficiency virus (HIV) infection, we determined the levels of serum thyroid hormones, serum binding proteins [thyroxine-binding globulin (TBG), cortisol-binding globulin (CBG), and sex hormone-binding globulin (SHBG)], and serum tumor necrosis factor (TNF) in HIV-seropositive subjects at different clinical stages. PATIENTS AND METHODS: Thirty-seven HIV-seropositive patients were studied: 7 at stage II, 13 at stage III, and 17 at stage IV (eight ambulatory and nine hospitalized) according to the Centers for Disease Control's criteria. RESULTS: As compared with stage II and stage III patients, stage IV patients had significantly higher mean TBG and total thyroxine (TT4) values, similar and normal total triiodothyronine (TT3) levels, and similar and abnormally low reverse triiodothyronine (rT3) concentrations. However, stage IV hospitalized patients had significantly lower TT3 values than stage IV ambulatory patients. In contrast to TBG, mean levels of CBG and SHBG were comparable in the three groups and within normal limits. For the whole population of HIV patients, there was a highly significant correlation between the CD4 lymphocyte count and TBG (r = -0.529, p less than 0.001) but not with CBG and SHBG levels. Finally, TNF values higher than 10 pg/mL were detected in six of the 17 stage IV patients and in only one of the 13 stage III patients (p = 0.059); elevated TNF levels correlated with a lower CD4 count (p less than 0.01) but not with serum TBG levels. CONCLUSION: The progression of HIV infection is associated with an elevation of serum TNF and TBG, but not of CBG or SHBG. HIV-infected patients have an unexpectedly normal TT3-low rT3 state.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The "low TBG syndrome" in patients on chronic hemodialysis: evolution after renal transplantation.

Patients on chronic hemodialysis may have a spuriously low TBG level, tentatively ascribed to uremia-induced changes in TBG immunoreactivity. In order to test this hypothesis, the effect of restoration of a normal renal function on TBG immunoreactivity was evaluated. TBG concentration was measured in 20 patients both by radioimmunoassay and by a T4-binding capacity assay, before, 4 and 10 months after a successful renal transplantation. Mean pretransplant TBG value measured by RIA was in the low normal range (1.60 +/- 0.14 mg/dl; normal limits 1.6-2.4 mg/dl). Twelve patients (60%) had TBG levels below 1.6 mg/dl (group I), while T4-binding capacity of TBG (TBC) measured in 7 of them was normal, so that the TBG/TBC ratio was characteristically reduced. The 8 remaining patients (group II) had TBG levels within or slightly above the normal range (mean value 2.26 +/- 0.17 mg/dl) and in the 5 tested patients, TBC and TBG/TBC ratio were normal. Four months after transplantation, mean TBG increased significantly in group I from 1.15 +/- 0.03 mg/dl before transplantation to 1.54 +/- 0.12 mg/dl (p less than 0.01). TBC increased also from 269 +/- 37.5 to 335 +/- 24 nmol/l (p less than 0.01) but to a significantly lesser extent than TBG (24% vs 48%, p less than 0.05). As a result, the TBG/TBC ratio returned to normal values, rising from 0.79 +/- 0.07 to 0.95 +/- 0.07 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Interference in thyrotropin (TSH) determination: falsely elevated TSH values in a transplanted patient.

We report a falsely elevated TSH value as determined by an immunoradiometric assay. The patient, a thyroidectomized woman on substitutive therapy, underwent a kidney transplantation. She was treated for transplant rejection with OKT 3 (Orthoclone), a mouse monoclonal antibody. The discrepancy between the TSH value (TSH-Riabead II, Abbott) and the thyroid hormones level led us to suspect the presence of antimouse antibodies in the serum of this patient. Indeed, human immunoglobulins directed against mouse IgG2a and IgG2b were detected. We repeated-the TSH determination in the presence of normal mouse serum (NMS) and obtained a true TSH value. Upon fractionation of the serum with protein-A chromatography, the falsely elevated TSH immunoreactivity was detected in the IgG fraction.

Animals↗
PubMed1989

[Serum level of neuron-specific enolase: value as tumor marker of microcellular bronchial cancer].

This study analyses retrospectively the plasma level of neuron-specific enolase (NSE) performed in 236 patients presenting for the diagnosis of a bronchopulmonary disease. Taking a cut off on 15 micrograms/L, 61 (64%) of the 95 patients sharing a small cell lung cancer (SCLC) (45% of those with a limited disease and 90% with an extensive disease) but 8 (13%) of 60 with a non small cell lung cancer patients and 0% of those with a benign bronchopulmonary disease showed an abnormal value of NSE. Therefore in this group of patients, the diagnosis of SCLC could be assessed with a sensitivity of 64% and a specificity of 94% in patients with an NSE plasma level above 15 micrograms/L. In addition, the interest of sequential dosages of NSE for the monitoring of SCLC patients is also stressed.

Biomarkers, Tumor↗
PubMed1989

Spontaneous healing of aneurysmal bone cysts. A report of three cases.

We report three cases of spontaneous healing of aneurysmal bone cysts (ABC). In one case histological material was obtained after resection of the already ossified expansile mass discovered as a lytic lesion seven months previously. In the two other patients, spontaneous ossification of a radiologically presumed ABC in the lytic and expansile phase was observed after nine and seven months respectively. The healed lesions have remained stable at 12, 32, and 36 months respectively. These findings suggest that when the diagnosis can be made with confidence, and the lesion is in a location and at a stage that does not entail any risk of fracture or compression, expectant management should be considered. Our three patients were aged 22, 19 and 18 years, older than usual for developing ABC. This is also true for many of the few other reported cases of spontaneous or almost spontaneous healing and suggests that ABC has a greater tendency to stabilise in older patients.

Adolescent↗
PubMed1989

Decreased serum TBG concentration in the face of normal T4-binding capacity in patients on hemodialysis.

Serum TBG concentrations were evaluated in 34 patients on regular hemodialysis. Mean serum TBG level measured by two different radioimmunoassays was markedly decreased (1.24 +/- 0.08 mg/dl - normal limits 1.6-2.4 mg/dl). Twenty-seven (79%) patients had values below 1.6 mg/dl, which contrasted in 21 of them with a lack of reciprocal elevation of T3RU values. By contrast, T4-binding capacity of TBG measured in 14 patients with low TBG concentration was normal, suggesting that the low TBG values were an artefact resulting from an altered immunoreactivity of the protein. In 2 patients with low TBG while on hemodialysis, TBG levels increased significantly after renal transplantation. This suggests that the "low TBG syndrome" (altered immunoreactivity in the face of normal T4-binding capacity) observed in patients on chronic hemodialysis is a consequence of uremia.

Adolescent↗
PubMed1988

Characterization of thyroid hormone receptors in human IM-9 lymphocytes.

Although putatively identified more than 10 years ago, thyroid hormone receptors in human tissues remain poorly characterized. As a first step towards understanding the mechanism of thyroid hormone action in man we have characterized T3 binding sites in nuclei of the human lymphoblastoid line, IM-9 cells. In whole cell experiments at 37 degrees C, nuclear binding of [125I]T3 was saturable (Kd 34 +/- 6 pmol/l) and of finite capacity (approximately equal to 350 sites/cell). The binding sites were extracted from a nuclear pellet by treatment with 0.4 mol/l KCl and sonication. Separation of bound from free [125I]T3 in the extracts was achieved using the calcium phosphate matrix, hydroxyapatite at a concentration of 0.3 ml of a 150 g/l slurry. Rectilinear Scatchard plots were obtained only when the hydroxyapatite was washed with a buffer containing 0.5% Triton X-100. Under these conditions T3 binding sites in the nuclear extracts were present at a concentration of 22.4 +/- 8.6 fmol/mg protein and showed an affinity of (Kd, room temperature) 140 +/- 10 pmol/l. The same assay system was used to determine the hierarchy of affinities for a range of natural and synthetic analogues. Calling T3 100, the order of potencies observed was: Triac, 500; 3,5-diiodo-3'-isopropylthyronine, 89; T4, 32; 3,5-dimethyl-3'isopropylthyronine 2; 3,5-T2, 0.7, rT3, 0.4; 3'5'-T2, less than 0.01. These results suggest that the T3 binding sites present in human IM-9 lymphocyte nuclei and extracts thereof are thyroid hormone receptors. These cells may be a useful tool to increase our understanding of human T3 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗