Long-standing goiter and hypothyroidism: an unusual presentation of a TSH-secreting adenoma.

A 63-year-old female patient was referred to our hospital in February 1994 for a pituitary tumor. On a previous examination, in 1973, she had a goiter, nonspecific symptoms and only an elevated serum T3. In 1984 she had become hypothyroid, her goiter had increased, serum T4 was 69 nmol/L, TSH 34.

Structure-activity relationships for substrates and inhibitors of pineal 5-hydroxytryptamine-N-acetyltransferase: preliminary studies.

Tryptamine, (1-naphthyl)ethylamine and phenethylamine derivatives were tested as substrates of ovine pineal serotonin-N-acetyl transferase (5-HT-NAT), a key enzyme involved in the synthesis of melatonin. Almost all of the indole derivatives possessed affinity similar to that of tryptamine (Km = 0.05 mM), while the substituted naphthalene and phenyl derivatives were less potent.

Design and synthesis of new naphthalenic derivatives as ligands for 2-[125I]iodomelatonin binding sites.

New melatonin-like agents were designed from the frameworks of 2,5-dimethoxyphenethylamine, an important structural moiety for the 5-HT receptor, and (2-methoxynaphthyl)-ethylamine. The compounds were synthesized by classical methods and evaluated in binding assays with chicken brain membranes using 2-[125I]iodomelatonin as the radioligand. Preliminary studies on the series of N-acyl-disubstituted phenethylamines showed the favorable role of the methoxy group in the ortho position of the side chain on the affinity for the receptor (Ki = 8 +/- 0.

Rapid washout of technetium-99m-MIBI from a large parathyroid adenoma.

We report a case of rapid 99mTc-methoxyisobutylisonitrile (MIBI) clearance from a parathyroid adenoma. A double-phase 99mTc-MIBI parathyroid scintigraphy was performed on a 62-yr-old female evaluated for primary hyperparathyroidism. A large parathyroid adenoma was visualized caudal to the left lobe of the thyroid gland with an unusually rapid washout of the tracer from tumor tissue.

Identification and characterization of a neuroretina-specific enhancer element in the quail Pax-6 (Pax-QNR) gene.

Using nuclear run-on assays, we showed that the tissue-specific expression of quail Pax-6 (Pax-QNR) P0-initiated mRNAs is due in part to regulation of the gene at the transcriptional level. Regulatory sequences governing neuroretina-specific expression of the P0-initiated mRNAs were investigated. By using reporter-based expression assays, we characterized a region within the Pax-QNR gene, located 7.

[Consensus and controversy on the treatment of differentiated thyroid cancers].

Differentiated thyroid carcinomas are the most common endocrine neoplasia. Because of their rather benign evolution, the treatment varies widely from minimal to aggressive interventions. Therefore there are considerable controversies as to the best therapeutic choice.

Determination of a PAF antagonist pharmacophore using combined Molecular Electrostatic Potential and Molecular Lipophilicity Potential.

PAF is a potent lipid mediator involved in many pathological disorders, such as platelet aggregation, immuno-inflammatory reactions, vascular disorders, septic shock and bronchoconstriction. We chose to study the electronic and lipophilic properties of eleven PAF antagonists, comprising five tetrahydrofuran derivatives, four hetrazepines, the ginkgolide BN-52021 and the pyrrolo-thiazole derivative RP-59227. A Molecular Electrostatic Potential (MEP) contour drawn at -25 kCal/Mol shows three electronegative areas in most compounds.

Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit.

The prognostic significance of the DNA content in Ewing's sarcoma: a retrospective cytophotometric and flow cytometric study.

The DNA content of the cell nuclei of Ewing's sarcoma was analysed by means of cytophotometry in situ with image analysis in Feulgen-stained sections in 37 patients, and by retrospective flow cytometry according to the method of Hedley in 26 patients. Different histogram patterns were obtained: normal unimodal or bimodal DNA distributions and abnormal DNA distributions with one or two stem lines, or an abnormal DNA distribution with no stem lines. Both methods enabled us to make a distinction between two groups of Ewing's sarcomas with a different prognosis.

The immunophenotype of Ewing's sarcoma. An immunohistochemical analysis.

Since 1963, 53 cases of Ewing's sarcoma have been diagnosed at the N. Goormaghtigh Institute of Pathological Anatomy. All tumours were classified according to their growth pattern as described by Kissane: diffuse, lobular or organoid, the latter with pseudorosettes, or belonging to the fillagree type.

Structural analysis by the comparative molecular field analysis method of the affinity of beta-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptors.

The affinities of 17 beta-adrenoreceptor antagonists for 5-HT1A and 5-HT1B receptors were evaluated in binding assays. A large range of Ki values (2-10,000 nM) was observed and ortho or meta substitution of the aromatic ring carrying the amino chain was implicated in the high affinity Ki values, whereas para substitution elicited a dramatic drop in activity. These variations were analyzed with two molecular design tools: the active analogue approach (AAA) and the new 3D-QSAR (quantitative structure activity relationship) method, comparative molecular field analysis (CoMFA).

Cross-resistances to antiviral drugs of IUdR-resistant HSV1 in rabbit keratitis and in vitro.

The emergence of cross-resistance to various antiviral drugs was investigated both in vivo and in vitro for herpes simplex virus type 1 (HSV1) resistant to idoxuridine (IUdR 0.24%) obtained by seven successive passages (from P0 to P7) in rabbit keratitis treated by IUdR. The viral population obtained at the seventh IUdR passage (P7) showed an activity of the thymidine kinase (TK) reduced to 5.

Glycation of human tissue and serum creatine kinase.

Human creatine kinase (CK) was demonstrated to be partly present as a glycated molecule. Sialic acid, galactose and sulfate were also found to be present on the molecule. The glycated forms were characterized by higher activation energies and were thermally unstable.

[Reversibility of IUdR resistance to sensitivity to an HSV1 strain in experimental keratitis in rabbits].

During 7 serial passages of Herpes Simplex Virus (HSV1) in rabbit cornea treated with idoxuridine (IUdR) (P1 to P7), the emergence of resistance had been obtained from P3. The reversion towards IUdR sensitivity has been investigated from either viral population P3 or P6 by 6 serial passages in rabbit cornea treated by Vaseline (V1 to V6). From viral population P3, the reversion to IUdR sensitivity has been obtained at V4.

Occurrence and characterization of acyclovir-resistant herpes simplex virus isolates: report on a two-year sensitivity screening survey.

For the past 2 years, a survey network was established for the screening of acyclovir (ACV)-resistant clinical isolates of herpes simplex virus (HSV). Among 889 strains tested for in vitro ACV sensitivity, 14 HSV-1 and 6 HSV-2 were resistant to ACV concentrations exceeding 3 micrograms/ml. These resistant isolates were most often obtained after prolonged ACV treatment of severely immunocompromised patients.

Emergence of cross-resistant herpes simplex virus following topical drug therapy in rabbit keratitis.

The acquisition of drug resistance in vivo was investigated by 7 serial passages (from P0 to P7) of herpes simplex virus (HSV-1) in rabbit cornea treated with either IUdR (idoxuridine), IDC (idoxycytidine), ACV (acyclovir), TFT (trifluridine), or Ara A (adenine arabinoside). Therapeutic failure was acquired gradually: at P3 for IUdR, at P4 for ACV and at P5 for TFT. At P7, viral thymidine kinase (TK) activity was reduced to 5.

Lipophilicity force field profile: an expressive visualization of the lipophilicity molecular potential gradient.

This paper proposes a new tool that allows us to see the following in the same frame: (1) 3D geometrical features of a molecule, and (2) pseudo-3D representation of the lipophilicity molecular potential. It thus becomes very easy to compare the lipophilicity molecular potential gradient of different molecules having the same pharmacological properties. An example of two structurally dissimilar anti-PAF molecules is given.

[Assay of plasma isosorbide dinitrate and its metabolites after oral administration of immediate and delayed-action forms].

This paper describes a kinetic comparative study of plasma concentrations of isosorbide dinitrate (ISDN) and its mononitrate derivatives (2-ISMN or 5-ISMN) after oral administration of a sustained release form of ISDN or a (non) sustained release form of 5-ISMN. The blood extracts determinations were performed by electron capture gas chromatography which is an accurate and sensitive method suitable for the quantitation of concentrations in the nanogram per ml range. The results are in good agreement with those of the literature.