Biomedical subjects
Publications and source records attributed to M Andreoli.
The paper reports a case of Morgagni-Larrey hernia observed by the authors. The etiopathogenesis is described and the importance of surgery is underlined even in asymptomatic cases in order to ensure a benign postoperative outcome.
In mouse thymocytes, a stereospecific saturable energy-dependent and ouabain-inhibitable system facilitates T3, but not T4, entry. We studied here the effect of sodium depletion on cellular uptake of thyroid hormones by mouse thymocytes. Time-course experiments indicated that extracellular sodium depletion reduced [125I]T3 uptake at each time studied. At equilibrium, the removal of extracellular sodium and its substitution with isoosmotic choline decreased saturable [125I]T3 uptake by 60 +/- 10%; this effect was dose dependent. The substitution of sodium with lithium, instead of choline, had no effect on the uptake process. [125I]T4 uptake was lower than that of [125I]T3 and not affected by sodium depletion. The half-maximal effect of sodium deprivation on [125I]T3 uptake was reached at an extracellular sodium concentration of about 40 mM. The variation of external pH influenced T3 accumulation by thymocytes. [125I]T3 progressively decreased from acid to alkaline pH under normal and sodium-depleted conditions; however, the sodium-dependent fraction was more than doubled at physiological pH compared to that at more acidic and more alkaline pH. The sodium ionophore monensin decreased T3 uptake by 51% at a concentration of 20 microM. These results indicated the existence of a sodium-related mechanism of T3 uptake into mouse thymocytes that does not operate for T4 uptake.
The correct diagnosis and an appropriate classification of hypothyroidism must be considered on the light of the most recent physiopathological and molecular information. Hypothyroidism is no longer regarded as the rare disease characterized by a myxedematous condition as described since one century ago. With the present improvement of the diagnostic tools the thyroid hypofunction now includes all those blunted forms that are classified as subclinical or latent hypothyroidism. Thus, the hypothyroid syndrome, previously considered a rare event in its overt form, reaches a prevalence of 14% in female aged over fifty years. Following a coherent, concise historical review, the influence of age, surgery, drugs and autoimmunity on the etiology of the disease are critically discussed. The early detection and treatment of congenital hypothyroidism, to avoid an irreversible damage of the central nervous system, by means of the screening on the paper spot is also stressed. Replacement therapy with synthetic levothyroxine has to be personalized, according to the age and other clinical conditions, and should be prescribed also in the treatment of subclinical hypothyroidism.
A microscale method, based on two-colour dye immunolabelling and flow sorting cytofluorometry, was used to characterize lymphocyte subsets in thyroid tissue specimens obtained by fine-needle aspiration (FNA) in 21 patients with autonomously functioning thyroid nodule (AFTN) and five patients with cold thyroid nodule (CTN). Inversion of the ratio between CD4+ and CD8+ lymphocytes, due to a relative increase of CD8+ cells, was found among intrathyroidal lymphocytes in AFTN patients. The abnormal lymphocyte subset distribution was not observed in the peripheral blood of the same group of patients. In patients with CTN the lymphocyte subset distribution was normal, both in the thyroid and in the peripheral blood. In AFTN patients, a significant correlation was observed between the decrease of intrathyroidal CD4+/CD8+ ratio and the increase of plasma thyroid hormone levels. Whether the immunological abnormalities found in AFTN could play a pathogenetic role in the clinical presentation and outcome of the disease remains to be established. The FNA-applied micromethod used in this study could be extended as a routine investigation to characterize the immunogenic substrate of thyroid disorders.
Thyroid hormone entry into the thymocyte, a thyroid hormone target, was investigated by incubating the cells with tracer amounts of [125I]L-T3. At 37 C T3 uptake was linear with time up to 2 min, and then approached a plateau. The specific T3 uptake, obtained by subtracting the uptake in the presence of excess unlabeled T3, represented 48 +/- 6% of the total at equilibrium. Unlabeled L-T4, D-T3, and triiodothyroacetic acid were less effective than L-T3 in reducing [125I]T3 uptake. Kinetic studies on the initial rate of T3 uptake indicated, for the saturable process, a maximum velocity of approximately 1 pmol/10(6) cells.min and a Km of approximately 0.8 nM. Lowering incubation temperature to 4 C resulted in a two thirds reduction of the total T3 uptake. Washout experiments indicated a different hormone release, being more rapid for cells incubated at 4 C than at 37 C; at 30 min 70% of labeled T3 was released when incubation was carried out at 4 C compared to only 35% after incubation at 37 C, indicating the major intracellular location of the hormone at the latter temperature. An energy requirement of T3 uptake in thymocytes was shown by sensitivity to oligomycin; the effect was dose dependent, showing a maximal decrease in specific uptake of 85%. The involvement of cation movement in the entry process of T3 was indicated by the sensitivity to ouabain. These results indicate the existence of a stereospecific, energy-dependent, saturable process for T3 entry in thymocytes.
Slow i.v. infusion of salmon calcitonin into normal women led to a transient increase in plasma concentrations of cyclic AMP and to a decrease in plasma calcium, which was maintained for at least 2 h. These responses were significantly reduced in the same patients after hysterectomy and ovariectomy. In contrast, maintenance of the ovaries at the time of surgery, or substitutive hormonal therapy, seemed to restore the sensitivity to exogenous calcitonin, suggesting a permissive role of ovarian steroids in the effect of calcitonin. The most likely explanation for this phenomenon is that these hormones influence either the number of calcitonin receptors or the coupling of the receptors to the functional unit of bone adenylate cyclase.
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1. The biosynthesis of 18-19S thyroglobulin has been studied in a larval and adult freshwater lamprey (Lampetra planeri Bl.). 2. In vivo and in vitro experiments have been performed by injecting into the coelomic cavity or by incubating branchial region labeled constituents of Tg of higher vertebrates (125I, [3H]leucine and various [3H]carbohydrates). 3. Larvae (ammocoetes) and adults incorporate all labels into thyroglobulin (18-19S Tg), containing a small proportion of labeled T3 and T4, as identified by paper chromatography, and very minute amounts of stable iodine. 4. In adults, the biosynthesis of 18-19S Tg proceeds much more rapidly and the labels are incorporated in higher percentage than in larvae. 5. The demonstration of the biosynthesis of the specific thyroid protein, 18-19S Tg, in larvae indicates that the biochemical mechanism of hormonogenesis is present in larval endostyle before the morphological differentiation of thyroid cells and follicles occurring during metamorphosis. 6. Some 18-19S Tg is apparently stored in the endostyle.
A Sepharose-coupled 19S human thyroglobulin has been used as an immunoadsorbent to isolate anti-thyroglobulin autoantibodies and to evaluate the antigen-antibody interactions. With the system proposed a high yield of active antibody molecules was obtained. It is possible to evaluate both the soluble and precipitating 'immunological interactions', thus avoiding the use of the double antibody technique.
The biosynthesis of thyroglobulin (Tg) in larva of a fresh-water lamprey, Lampetra planeri B1. has been established. This glycoprotein presents the same characters as in thyroid follicles of adult lampreys, as shown by its 18-19 S sedimentation coefficient and by the incorporation (in vivo and in vitro experiments of 4, 12, 72 h) of 125I, 3H-leucine and 3H-galactose. 3-8 S fractions and a 12 S monomer are the precursors of the 18-19 S protein. Total I % of Tg is very low (0.002 %) ; about 5 % of 125I are present in thyroid hormones (T3 and T4) in the 125I-labeled protein. The biosynthesis of 18-19 S Tg proceeds in larvs before the morphological differentiation of thyroid cells and follicles after metamorphosis. However, the biosynthesis of this protein is much slower in the endostyle of larvs, in which a primitive mechanism of storage is poorly efficient, compared to the accumulation of Tg in the colloid of the follicles of adults.
Thyroglobulins (TG) from a "hot" human thyroid nodule and from Fisher rats have been purified and the effects of progressive removal of sialic acid and galactose on the immunoreactive properties of the proteins were studied. Terminal sialic acid and galactose were released by stepwise hydrolysis with neuraminidase and beta-galactosidase. Agalacto-TG shows a slower electrophoretic mobility than native TG, but in polyacrylamide gel electrophoresis and immunoelectrophoresis it migrates in the same position as asialo-TG. In immunodiffusion agalacto-TG forms a spur with native TG and asialo-TG when tested against anti 19S native TG or anti-asialo-TG sera. It is thus shown that galactose in the terminal environment of the oligosaccharide chains of thyroglobulin is essential for the structural groups involved in the antigenic properties of thyroglobulin.
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Thyroglobuline (Tg) biosynthesis has been studied in an adult fresh water lamprey Lampetra planeri (Bloch), by injection in coelomic cavity or by in vitro incorporation in follicles of branchial region of various radioactive labels: 125I-, 3H-leucine, 3H-mannose, 3H-galactose, N-acetyl mannosamine and 3H-N-acetylglucosamine. Labelling by all theses substances, present in Tg of mammals, proceeds efficiently in two hours. It has been demonstrated that the cyclostome studied synthetizes a 18 S iodinated glycoprotein analogous to Tg of higher vertebrates by its molecular size. It contains all the same hexose and N-acetyl derivatives of these in its sugar moiety and the same iodinated aminoacids. Purified 18 S Tg of the lamprey has been prepared; it is very poor in iodine (127I) and has a very low T3 and T4 content.
Studies on "cold" and "hot" nodules from human thyroid gland have been carried out to investigate thyroglobulin biosynthesis and to correlate carbohydrates incorporation and thyroid hormone formation in thyroglobulin. The aim of the investigation was to ascertain the role of carbohydrates of the protein molecule in its migration to the iodinating site of the cell. Thyroid slices from two cases with "cold" and two with "hot" nodules were incubated for 30 to 120 min with [3H]leucine, [3H]carbohydrates (ManNAc, Gal, Man, GlcNAc, GalNAc) and 125I. Soluble and particulate iodoproteins, solubilized by digitonin, were identified by density gradient centrifugation and immunoprecipitation; following hydrolysis carbohydrates and iodothyronines were identified by paper chromatography and chemically determined. While the rate of leucine incorporation into TG increased with time in both "cold" and "hot" nodules, the "cold" nodule, with respect to the "hot" tissue, showed: much lower efficiency incorporating carbohydrates and iodine into TG; lower thyroid/medium ratio of radioiodine; less total soluble protein and soluble TG; more particulate protein and solubilized TG; 1/3 of the carbohydrate and iodine chemical content; only minute amounts of labeled iodothyronines in TG compared to normal levels in "hot" tissue. The formation of thyroid hormone, in enzymatically iodinated TG, and the iodinating activity of the 105,000 X g pellet, incubated with low iodine TG, were similar in both "cold" and "hot" tissues. These results demonstrate that the "cold" nodule is able to synthesize thyroglobulin but the protein is defective in its carbohydrate content. The deficient iodine transport into "cold" tissue and impaired hormonal synthesis are confirmed. The incomplete incorporation of carbohydrates into thyroglobulin in the "cold" nodule could be important for the maturation and migration of the molecule to the iodinating site of the cell
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