Specific staining of the thyroid follicular cell apical membrane by nitroblue tetrazolium.

Nitroblue tetrazolium (NBT) has been widely used to demonstrate redox systems, particularly in phagocytizing polymorphonuclear leukocytes. Based on the striking similarities between redox metabolism in leukocytes and in the thyroid, we studied NBT reduction by microscopic techniques and NBT effects in thyroid metabolism in dog-thyroid slices in vitro. We observed specific localization of NBT reduction product along the apical membrane of the follicular cell. Hence, NBT is a potentially useful market of thyroid-cell polarity.

[Fine-needle aspiration (F.N.A.) of thyroid cold nodules (author's transl)]. / Place de la ponction á l'aiguille fine (P.A.F.) dans le diagnostic clinique du nodule thyroïdien froid.

In a retrospective study of 100 patients operated on between 1974 and 1979 in our institution for thyroid cold nodules, an 8% incidence of thyroid cancer was found at surgery. Since 1979, F.N.A. was performed in 160 patients with thyroid cold nodules. Adequate cytological material was aspirated in 90% (144) of the cases; of those, a benign cytological lesion was diagnosed in 128 (89%) and suspicion of cancer in 16 (11%). To date fifty-one patients were operated: 41 with benign cytology and 10 with cancer suspicion; benignity was confirmed in 39/41 cases with benign cytology and malignity in 5/10 with suspect cytology. In conclusion, clinical diagnosis of thyroid cold nodules is greatly improved by the use of F.N.A. Despite the limitations of the technique, preoperative suspicion of cancer was increased 7-fold. Caution is recommended in the follow-up cases with benign cytology since, in these preliminary results, 2 false-negatives were found.

Mauriac syndrome: three cases with retinal angiofluorescein study.

Three children with features of the Mauriac syndrome have been studied. Ocular complications, mainly characterized by increased capillary permeability have been demonstrated by fluorescein angiography. A decreased proximal tubular beta 2-microglobulin reabsorption has been found in one patient, and in another one, there was a slowed sensory nerve condition velocity. A liver biopsy, performed in one patient, has shown numerous fat filled cells and intralysosomal lipofuscin storage. No hormonal disturbance, which could explain the growth reardation, has been found. Bad metabolic control of diabetes could be responsible for all the anomalies of Mauriac syndrome.

Cellular toxicity of gentamicin.

Subconjunctival injections of gentamicin induced a lysosomal storage process within the conjunctival fibroblasts in rats, rabbits, and humans. Under electron microscopy, the accumulated substance was composed of a granular material and pleomorphic lamellar structures, corresponding to the presence of complex lipids. In animals, the other ocular tissues as well as the cells reached through the bloodstream remained unaffected, except the proximal convoluted tubules of the kidneys, where important lesions were evident. Although human kidneys were not examined in our study, we believe they might present similar alterations.

Hormonal secretion by hyperactive thyroid cells is not secondary to apical phagocytosis.

Hyperactive dog thyroids were prepared by repeated TSH stimulation in vivo. Butanol-extractable 125I (BE125I) release in vitro from slices and hormonal secretion in vivo in the thyroid vein was enhanced. Apical pseudopods and colloid droplets were very infrequent in such hyperactive thyroids. Moreover, BE125I release was insensitive to cytochalasin B, to inhibitors of microtubules, and to metabolic inhibitors, and decreased only with temperature. Our data demonstrate that hormonal secretion by hyperactive thyroids is not secondary to apical phagocytosis (i.e. macropinocytosis). Micropinocytosis or intraluminal hydrolysis of thyroglobulin are suggested as first step of the secretory process.

Kinetics of dog thyroid secretion in vitro.

The time sequence of radioiodine sequestration and secretion (BE131I) have been compared in dog thyroid slices prelabeled with 131I in vivo and incubated in vitro with or without TSH. Sequestration has been taken to be the amount of radioiodine present in phagocytic vacuoles or colloid droplets; the TSH or (Bu)2cAMP stimulation of the basal values was suppressed by endocytosis blocking drugs. TSH induced a sequestrated radioactivity (S) after 5 min and a stimulated secretion after 20 min. The secretion rate was constant: 1%/h (mean +/- SD = 1.0 +/- 0.4; n = 7) of the total radioactivity of the slices. At equilibrium, S was constant and equal to less than 1% of the total radioactivity. The half-life of S, assuming a disappearance rate proportional to S, was 26 min (26 +/- 4; n = 5); assuming a disappearance rate independent of S, the lifetime was 44 min (44 +/- 7; n = 6). At the steady state, the limiting step of maximally stimulated secretion was the hydrolysis of the sequestrated radioactivity and endocytosis rate was equal to secretion rate. Without TSH, a constant BEI release (0.23% +/- 0.07%/h; n = 7), insensitive to cytochalasin B, was observed, which corresponded to basal secretion.

Uncoupling by cooling of secretion and adenosine 3',5'-monophosphate accumulation in stimulated dog thyroid slices.

Thyroid metabolism undergoes general activation in the presence of TSH. Secretion, [1-14C]-glucose oxidation, protein iodination, and cyclic AMP (cAMP) accumulation are stimulated. In intact tissue, it is difficult to dissociate effects of cAMP itself and effects secondary to cAMP-induced secretion. We report herein that cooling to 20 C dissociates the action of TSH on secretion from all its other effects. At this temperature, TSH stimulation of secretion was completely inhibited whereas cAMP accumulation was enhanced. The TSH effect on [1-14C]glucose oxidation was maintained and its action on protein iodination was diminished but not abolished. The ATP content was not decreased. The mechanism of action of cooling was investigated. No pseudopod formation of intracellular colloid droplets were observed by scanning electron microscopy and transmission electron microscopy, thus indicating that the inhibition affects the first step of secretion, i.e., colloid phagocytosis. Microtubules were not seen at 2 C but were normally present at 20 C. The data are compatible with the hypothesis that inhibition of phagocytosis at 20 C could be a consequence of a lipid phase transition in the membrane.

[Thyroid secretion in experimental hyperplasia (author's transl)]. / La sécrétion thyroïdienne dans l'hyperplasie expérimentale.

Hyperactive dog thyroids were prepared by repeated TSH stimulation in vivo. Butanol extractable 125iodine (BE 125I) release in vitro from such hyperactive thyroid slices was enhanced when compared with resting slices. Apical pseudopods an colloid droplets were exceptional in such hyperactive thyroids. Moreover, BE125I release was intensitive to cytochalasin B, microtubules and metabolic inhibitors, and decreased only with temperature. Our data demonstrate that hormonal secretion by hyperactive thyroids is not secondary to apical phagocytosis of colloid droplets.

[Hypertrophy and hyperplasia of hyperactive thyroid cells: hormonal secretion is independent of apical phagocytosis (author's transl)]. / Hypertrophie et hyperplasie des cellules thyroïdiennes hyperactives: la sécrétion hormonale est indépendante de la phagocytose apicale.

Hyperactive thyroid are obtained by daily injections of TSH 15 I.U. I.M. in dogs for 8 days. The high secretion rate of butanol-extractible iodide (BE125I) in vitro by prelabelled slices is not related to apical phagocytosis (lack of apical pseudopods and intracellular colloid droplets, insensitivity to cytochalasin, vinblastine, vincristine and colchicine). The secretory process is insensitive to metabolic inhibitors, decreases exponentially with the temperature without step transition and could be related to micropinocytosis.

New ultrastructural features on the cream hamster thyroid with special reference to the second kind of follicle.

The thyroid cells of the cream hamster, characterized by abundance of microtubules and stratification of the organelles, undergo a particular evolution when the animals grow older. These changes are characterized by an increase of the number of lysosomes which in extreme cases become so prominent that they occupy the whole cytoplasm of the cell which thus loses its organelle stratification. As in other species, cream hamster thyroid contains so-called ultimobranchial follicles made up of at least six cell types: fibrillar dark and light cells, parafollicular cells, ciliated cells, vesicular cells, and cells with myelinic inclusions. The ultrastructure of these follicles in the cream hamster represents a mixture of the ultrastructural characteristics of the same follicles encountered in the rat and the mouse thyroid. Here also mixed follicles are seen. Nevertheless vesicular cells present such abundant "secretion granules" that the question arises as to whether these follicles produce a special secretion and perhaps a new hormone. Incubation of cream hamster thyroids in the prescence of vincristine induces vanishing of microtubules, formation of paracrystalline structures, and loss of stratification of the organelles. Although these last effects might be due to some specific toxic effect of the drug, it is suggested that the disappearing of the organelle stratification might result from a specific vincristine-induced disaggregation of the microtubules acting as a cytoskeleton.

Intracerebral calcifications appearing during the course of acute lymphocytic leukemia treated with methotrexate and X-rays.

The authors present the case of a child aged 7 years who suffered from relapsing acute lymphocytic leukemia. Treatment consisting mainly of oral and intrathecal methotrexate and x-ray therapy produced remission of the hematologic symptoms. Three years after the onset of the leukemia, mental deterioration gradually appeared. Radiography of the skull revealed diffuse bilateral calcium deposits in both cerebral and cerebellar hemispheres. Four years after the onset of the disease, a hematologic relapse occurred. Behavioral disorders became more severe and the child died after a period of seizures and unconsciousness. The main pathologic data obtained by the study of a brain biopsy and after a complete postmortem examination consisted of calcifications located bilaterally in the cerebral and cerebellar cortex. No signs of leukemia were present. Cerebral calcification is an extremely rare complication in the course of the therapy of lymphocytic leukemia. Its possible causes are discussed.

Ultrastructural aspects of the thyroid in a case of human congenital goitre with cretinism.

Transmission electron microscope and scanning electron microscope studies in a case of congenital goitre associated with cretinism revealed the existence of two cell types: the first with rounded endoplasmic cisternae and normal lysosomes; the second characterized by an abundance of lysosomes and/or lipofuscin granules. Intermediary aspects suggested that the second cell type was the progeny of the first type. As colloid droplets and apical pseudopods engulfing colloid were nearly absent, and as NBE127I was elevated in the plasma, it is suggested that iodoprotein secretion occurred by a process different from colloid phagocytosis as observed after acute TSH stimulation.