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G Filaci,
M Rizzi,
M Setti,
D Fenoglio,
M Fravega,
M Basso,
G Ansaldo,
P Ceppa,
G Borgonovo,
G Murdaca,
F Ferrera,
A Picciotto,
R Fiocca, G Torre,
F Indiveri
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ABSTRACT: Recent studies on regulatory lymphocytes demonstrate that CD8(+) T suppressor (Ts) cells may have great relevance in controlling immune system homeostasis and avoiding development of chronic inflammatory diseases. Among the three subpopulations of CD8(+) Ts cells so far recognized in humans, the type 2 (non-antigen-specific) cell is characterized by the capacity to inhibit both T cell proliferation and cytotoxic T lymphocyte activity through secretion of soluble factors. Previous work has shown the impairment of in vitro generation of type 2 CD8(+) Ts cells from the peripheral blood of relapsed patients with multiple sclerosis, systemic lupus erythematosus, or systemic sclerosis. Here, similar findings are demonstrated for patients with human immunodeficiency virus or chronic hepatitis C virus infection. Furthermore, the presence of type 2 CD8(+) Ts cells infiltrating diseased tissues in patients with autoimmune thyroiditis or cancer is shown. Collectively, these findings suggest that type 2 CD8(+) Ts cells may be involved in the control of pathologic chronic immune responses, contributing in some cases to the pathogenesis of the disease.
Annals of the New York Academy of Sciences 07/2005; 1050:115-23. · 3.15 Impact Factor
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ABSTRACT: Cultured thyroid epithelial cells can be induced to express intercellular adhesion molecule-1 (ICAM-1, or CD54). However, constitutive follicular expression of ICAM-1 has been reported only in thyroid autoimmunity. We evaluated the expression of ICAM-1 mRNA and protein on thyroid tissue from different autoimmune thyroid diseases, and its relationship with other immunologically relevant surface markers, namely costimulatory molecules of B7 family. Thyroid tissue sections were obtained by surgically removed thyroid glands from 6 patients with Hashimoto's thyroiditis (HT), 6 with Graves' disease (GD) and 3 with multinodular nontoxic goiter. We used in situ hybridization to localize ICAM-1 mRNA, and immunohistochemical analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) method. We showed a clear hybridization pattern, localized in follicular cells, in sections of glands with HT. The hybridization pattern was far less pronounced in GD: no staining was apparent on follicular cells. These results were strictly consistent with those obtained by means of immunohistochemistry. Moreover, double-staining experiments demonstrated colocalization of ICAM-1 and B7.1 molecules in HT, whereas no B7.1 expression was observed in Graves' or in non-autoimmune thyroid diseases. These data agree with the hypothesis of distinct immunoregulatory phenomena and effector mechanisms in the 2 main autoimmune thyroid diseases.
Journal of endocrinological investigation 04/2002; 25(3):289-95. · 1.57 Impact Factor
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ABSTRACT: It is known that factors other than thyroid-stimulating hormone, such as insulin-like growth factor-I (IGF-I) and epidermal growth factor, have a goitrogenic effect. It has been established that insulin-like growth factor-binding proteins (IGFBPs) may play a role as autocrine/paracrine factors in regulating the local actions of IGFs. Both an inhibitory and a stimulatory effect for different IGFBPs have been shown in several cell systems. The aim of this study was to assess the involvement of IGFBPs in the goitrogenic process in patients with goiter recurrence.
The IGFBP-1 and -3 content in normal and nodular tissues obtained at the time of thyroidectomy from 10 patients with recurrent goiters, unresponsive to thyroid-stimulating hormone suppressive therapy, was studied. In all patients, a fragment of normal tissue was also obtained. The IGF-I, IGFBP-1, and -3 content was evaluated by specific immunoassays and/or immunoblotting with anti-IGFBP specific antiserum.
The IGF-I content was significantly higher (P < .05) in nodular tissues (8.0 +/- 1.6 ng/g of tissue) than what was found in normal tissue (4.8 +/- 0.9 ng/g). Radioimmunoassay IGFBP-3 concentration in nodular tissue was 111.5 +/- 18.2 ng/g significantly higher (P < .001) than values found in normal tissue (77.5 +/- 18.6 ng/g). By immunoblot, IGFBP-1 appeared higher in all but 1 nodular tissue.
These data raise the possibility that IGFBPs are important in the proliferative activities entailed in the goitrogenic process. Three mechanisms are potentially involved: (1) reduction of the potency of locally produced IGF peptide to downregulate type I receptors (potentiating effect on the autocrine/paracrine mitogenic action of IGFs); (2) increase of the IGF-I tissue concentration restraining its passage to circulation; and (3) protection of IGF-I from degradation. Further studies are needed to define a more precise link between these factors and the recurrence of goiter.
Surgery 01/2000; 127(1):99-103. · 3.10 Impact Factor
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ABSTRACT: The molecules of the B7 family play a major role in T-lymphocyte costimulation through interaction with their counterreceptors CD28 and CTLA4. In the present study, we analyzed the possible expression of B7 molecules on surgically removed thyroid tissue of patients with autoimmune [Hashimoto's thyroiditis (HT) or Graves' disease (GD)] or nonautoimmune [nontoxic goiter (NTG) or papillary cancer (PC)] thyroid diseases. We found clear positivity of thyroid follicular cells for B7.1 in HT but not in GD, nor in nonautoimmune specimens (NTG, PC) using in situ analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Double immunostaining experiments in combination with an anti-human thyroglobulin antibody confirmed follicular B7.1 localization. On the contrary, no follicular B7.2 expression was observed in any specimen analyzed. These findings were confirmed by immunofluorescence flow cytometry on isolated follicular cells. The cytokines IL1beta and LPS were able to induce de novo B7.1 expression on cultured thyroid follicular cells. Intrathyroid T cells proved responsive to stimulation via the B7 ligand CD28, even in the absence of IL2. Moreover preliminary evidence was obtained for an inhibitory effect of anti-B7.1 mAb on T-cell proliferation in coculture with isolated thyroid follicular cells. It is conceivable that in HT, expression of B7.1 on follicular cells, together with MHC class II antigens and ICAM1, could provide a local costimulatory signal for T-lymphocyte differentiation toward the type 1 cytokine secretion pattern and maintenance of the autoimmune process.
Journal of Clinical Endocrinology & Metabolism 12/1998; 83(11):4130-9. · 6.50 Impact Factor
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ABSTRACT: To find out by studying a homogeneous group of patients whether euthyroidism is achievable by surgical treatment of diffuse toxic goitre.
Retrospective study.
Teaching hospital, Italy.
128 of the 152 patients operated on for diffuse toxic goitre during the period January 1971-December 1994 and followed up for a median of 83 months (range 6-289). INTERVENTION. Standard subtotal thyroidectomy.
Operative mortality, recurrence, hypothyroidism and late complications.
There were no operative deaths. After 10 years follow up, 11 patients (9%) had developed recurrences and 61 (48%) were euthyroid. In the univariate analysis the risk of hypothyroidism was significantly associated with the year of operation (p = 0.04), the duration of symptoms (p < 0.01), and the degree of lymphocytic infiltration (p < 0.01). The last two were confirmed by multivariate analysis.
Subtotal thyroidectomy seems to be an effective treatment of diffuse toxic goitre as a stable euthyroid state can be achieved in nearly half the patients after a prolonged follow up.
The European Journal of Surgery 07/1998; 164(7):495-500.
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Journal of experimental & clinical cancer research: CR 04/1998; 17(1):109-12. · 1.50 Impact Factor
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ABSTRACT: We report a case of mucoepidermoid carcinoma of the thyroid gland. The simultaneous association of papillary and mucoepidermoid carcinoma in a Hashimoto's thyroiditis makes the present observation unusual. Surgery was limited due to local extension of the neoplasm. The patient consequently underwent external radiotherapy followed by radiometabolic therapy. The patient survived 11 months after diagnosis. As far as the histogenesis of the neoplasm is concerned, we believe that mucoepidermoid areas correspond to squamous and mucinous metaplasia of a preexisting papillary carcinoma. Transition areas between elements morphologically characteristic of both neoplasms were observed. Histochemical and immunohistochemical studies confirmed the diagnosis of a carcinoma with multiple aspects showing a focal positive reaction for thyroglobulin or keratin antisera. Therefore, this demonstrates different functional activities of the neoplastic cells. There is still debate about adjuvant therapies, the results of which appear for the moment very poor.
The American surgeon 04/1998; 64(4):307-11. · 1.28 Impact Factor
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ABSTRACT: Between 1968 and 1991, 190 patients (51 men, 139 women) with a mean age of 46.3 years underwent surgery for differentiated thyroid cancer (148 papillary and 42 follicular carcinomas). In 29.5% of the cases a concomitant goitre was histologically demonstrated. These patients were significantly older (mean: 54.7 years) (P<0.01). The patients who had previously received cervical radiotherapy were significantly younger (mean: 29.7 years) (P<0.01). The analysis of historical and clinical findings failed to identify predictive factors of biological aggressiveness. Hyperthyroidism occurred in 5.7% of patients: this subgroup did not show any difference in clinical behaviour. Occult carcinoma (14.7%) and multifocality (9.4%) were found more frequently in the glands with a pre-existent goitre (P<0.05), but the clinical significance of these aspects is uncertain. The surgical treatment of choice was total thyroidectomy (135 patients); more conservative procedures were performed only in younger patients with small lesions, without a difference in survival. Post-operatively a permanent recurrent laryngeal nerve injury occurred in four patients (2.1%) and nine patients (4.7%) required a permanent calcium supplementation. Among patients in follow-up (91.6%), those who underwent a total thyroidectomy were studied using a total body scinti scan. A poor prognosis was associated with age (>40 years), pT, stage, pM and symptomatic metastases.
European Journal of Surgical Oncology 06/1996; 22(3):276-81. · 2.50 Impact Factor
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ABSTRACT: Between 1968 and 1991, 237 patients underwent thyroidectomy for substernal goiter. Sixteen of them presented malignancies (6.8%). Mean age of the 159 women and 78 men was 57.7 years. Twenty-five patients had undergone previous thyroid surgery. The initial symptoms were cervical mass (72%), compression (16.2%), hyperthyroidism (13.1%), hypothyroidism (1.3%), and 5.5 per cent were asymptomatic. Most patients had long-standing goiter (mean duration: 12.9 yrs). All but eight operations were performed through a cervical incision. There were two postoperative deaths (0.8%), both in patients with advanced neoplasms. Early postoperative complications were hemorrhage (0.8%), dysphonia (4.6%), and transient hypocalcemia (2.9%). Five patients (2.1%) required tracheotomy. Complications were more frequent after total thyroidectomy than partial resection (P < 0.05), after surgery for malignancy than for benign disease (P < 0.05), and in complex than in simple forms (P < 0.05). One hundred ninety-four patients were followed after surgery; dyspnea was found in two patients (1.0%), dysphonia in seven (3.6%), and hypoparathyroidism in one. Analysis of our data indicates that 1) substernal goiter arose in elderly patients more than a decade later than cervical goiter; 2) goiters with a "complex" endothoracic development had an increased rate of short and long term complications; 3) cancer occurred in a significant number of patients, without any specific symptoms of malignancy; 4) the group of patients with hyperthyroidism was characterized by a significantly longer clinical history than euthyroid patients; 5) nearly all substernal goiters could be approached through a cervical collar incision; 6) the morbidity and mortality were low also after sternotomy.(ABSTRACT TRUNCATED AT 250 WORDS)
The American surgeon 09/1995; 61(9):826-31. · 1.28 Impact Factor
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ABSTRACT: The Riedel's thyroiditis is an uncommon form of chronic thyroiditis characterized by an invasive fibrosclerosis of the gland, often involving the surrounding tissues. Usually, the only possible treatment is the surgical decompression of the tissues. We describe a case of aggressive Riedel's thyroiditis with severe compression and dislocation of trachea and esophagus. The surgical approach was uneffective, while an "ex juvantibus" steroid treatment, resulted in a dramatic regression of fibrosclerosis and a complete clinical remission. This report points out the possible effectiveness of corticosteroids in the treatment of selective disorders involving increased fibrogenesis.
Journal of endocrinological investigation 05/1995; 18(4):305-7. · 1.57 Impact Factor
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ABSTRACT: The purpose of this study was to determine the presence of cytosolic and nuclear androgen receptors (AR) in both normal and nodular thyroid tissues from twelve women and six men. Samples of benign thyroid nodules and corresponding surrounding normal tissue were processed by the single saturation point assay, using [3H] R1881 ([3H] Methyltrienolone) at final concentration of 5 nM. The results show the presence of AR (cytosolic and/or nuclear) in all examined tissue samples. The nuclear AR content was higher (p less than 0.01) in normal rather than in nodular thyroid tissues. The same pattern was observed when nuclear AR were analyzed according to the sex. In addition, nuclear AR content was significantly (p less than 0.05) higher in normal thyroid tissue from men than from women. Our data suggest an androgen influence on thyroid tissue. If androgens are supposed to exert an antagonist role on estrogen actions also in thyroid tissue, the presence of higher nuclear AR concentration in the male rather than in the female normal thyroid may justify the lower incidence of thyroid diseases in men. Moreover, the lower AR levels found in male as well as in female nodular and goitrous tissues support the hypothesis that androgens may act with an antagonist mechanism on thyroid growth.
Journal of endocrinological investigation 02/1991; 14(1):31-5. · 1.57 Impact Factor
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ABSTRACT: We investigated the phenotype and function of thyroid tumor-, metastatic lymph node-, and peripheral blood-derived T lymphocytes of four patients with papillary thyroid cancer. Both phenotypic analysis of freshly isolated cells and clonal analysis, using a high efficiency cloning technique, were performed. For comparison, intrathyroid and peripheral blood T lymphocytes derived from patients with autoimmune thyroid diseases (Graves' disease and Hashimoto's thyroiditis) have been studied. In papillary cancer, the phenotype of thyroid and lymph node-derived T lymphocytes did not differ from that of peripheral blood lymphocytes of the same patients or lymphocytes from normal peripheral blood. At variance with respect to autoimmune thyroid disease, activation markers were poorly represented. The functional analysis of T cell clones showed similar proportions of interleukin-2-producing (helper-inducer) clones in thyroid, lymph node, and peripheral blood, slightly lower than in Hashimoto's thyroiditis and slightly higher than in Graves' disease. With regard to effector function, we found lower proportion of clones with cytolytic activity in a lectin-dependent assay compared to that in Hashimoto's thyroiditis. Interestingly, however, the proportions of cytolytic clones displaying cytolytic activity against the neoplastic cell line K562 (natural killer-like activity) or fresh unrelated tumor cells (lymphokine-activated killer activity) were relatively high in thyroid cancer infiltrates.
Journal of Clinical Endocrinology & Metabolism 11/1989; 69(4):832-6. · 6.50 Impact Factor
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ABSTRACT: Estradiol and progesterone receptor proteins (ER, PgR) have been demonstrated in neoplastic and non-neoplastic human thyroid. The aim of this study was to determine the sexual steroid receptor content of pathological non-malignant thyroid (solitary adenoma, simple nontoxic goiter), and the adjacent normal tissue of the thyroid. The results show the presence of ER and PgR (cytosolic and/or nuclear) in most of examined tissues both pathological and normal. Low levels of steroid receptors are found in the cytosol fraction, whereas the receptor content is higher in the nuclear fraction. No correlation could be found between receptor levels and patients' age, menstrual state in females, and sexual steroid circulating hormones. A significant difference has been observed between adenomas and simple goiters (p less than 0.001) in the nuclear ER, and between normal tissue surrounding adenoma and normal tissue in goiters (p less than 0.05). This result suggests that estradiol and progesterone receptors are present in thyroid tissue and may have a physiological function.
Journal of endocrinological investigation 10/1989; 12(8):565-70. · 1.57 Impact Factor
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ABSTRACT: T cells isolated from thyroid tissue and peripheral blood of 2 patients with Hashimoto's thyroiditis were studied by a high cloning efficiency microculture technique. Clonal efficiencies of 37 and 24% were obtained from thyroid-derived T cell cultures, while 40 and 90% efficiencies resulted from peripheral-blood-derived cultures. A prevalence of T4-/T8+ T cell clones were found in thyroid infiltrates. The functional analysis of the clones demonstrated significantly higher proportions of clones with cytolytic activity in a lectin-dependent assay in thyroid-derived microcultures, as compared to peripheral blood-derived ones. The proportion of clones displaying natural-killer-like activity was increased in 1 patient only. Cytolytic activity was displayed not only by all T4-/T8+, but also by several T4+/T8- intrathyroid clones. Remarkable proportions of cytolytic clones were also able to release interleukin-2 upon phytohemagglutinin stimulation. Finally, the proportion of T cell clones able to release gamma-interferon following mitogen stimulation was significantly higher in thyroid- vs. peripheral-blood-derived microcultures. These results provide further data about the possible pathogenetical role of both regulatory and effector T lymphocytes in human autoimmune thyroiditis.
International archives of allergy and applied immunology 02/1987; 82(2):141-6.
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ABSTRACT: A phenotypic analysis of T cells infiltrating the thyroid of patients with autoimmune thyroid disease (both Graves' disease and Hashimoto's thyroiditis) was performed. T lymphocytes were purified from mononuclear cells extracted from surgically removed tissue. The following markers were evaluated: la antigens, MLR4 antigen (expressed on activated T cells) 5/9 antigen (expressed on a subset of lymphocytes containing the whole "helper-inducer" activity in vitro), Fc gamma-receptors, B9 antigen (expressed by cytotoxic, or precursor of cytotoxic, T cells). We observed increased percentages of 5/9-, MLR4- and la-positive T cells with respect to peripheral blood in both HT and GD: on the contrary, in specimens from nonautoimmune thyroid diseases mononuclear infiltrate was minimal, and even T cell evaluation was not possible. In addition, B9- and Fc gamma-positive T cells were increased in Hashimoto's, but not in Graves' thyroid tissue, thus suggesting a different role of cytotoxic effector mechanisms in the two diseases.
Journal of endocrinological investigation 01/1985; 7(6):641-5. · 1.57 Impact Factor
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ABSTRACT: The serum concentration of circulating somatomedins was measured in the blood of healthy donors and subjects with hepatic cirrhosis, and in culture media from in vitro explants of healthy and cirrhotic human liver. Serum levels of somatomedin bioactivity were significantly lower in cirrhotic subjects (0.42 +/- 0.03 U/ml; M +/- SEM) compared with age matched controls (0.99 +/- 0.03 U/ml). Radioreceptor assay of somatomedin concentrations confirmed this reduction in cirrhotic patients (0.89 +/- 0.06 U/ml) compared with controls (1.32 +/- 0.05 U/ml). A parallel reduction in somatomedin circulating binding ability was also observed (99.43 +/- 7.28% in cirrhotic and 123.5% +/- 10.8% in normal subjects). In vitro explants from normal human liver tissue produced a significant increase (0.57 +/- 0.09 U/ml) in somatomedin bioactivity contained in the medium (0.29 +/- 0.06 U/ml), while a decreased bioactivity (0.12 +/- 0.06 U/ml) was observed with explants of cirrhotic livers. These results support a role of liver in the biosynthesis of both somatomedin and somatomedin binding protein.
Hormone and Metabolic Research 01/1985; 16(12):663-6. · 2.19 Impact Factor
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The Lancet 06/1983; 1(8334):1163. · 38.28 Impact Factor
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ABSTRACT: Parathyroid cysts are rare, representing 1% of all neck swellings. A correct preoperative diagnosis is rarely formulated, especially because of the non-specific clinical and ultrasonographic findings; for this reason, patients are often submitted to surgery for thyroid nodules. In the present report we describe a case where the preoperative diagnosis was correctly formulated following the aspiration and PTH assay of clear, colorless, watery fluid from the cyst. While cyst aspiration is considered the elective treatment for these lesions, recurrences being uncommon, surgery was indicated in the present case because of two recurrences after aspiration and the onset of compressive symptoms. Cystic masses of the neck should be accurately diagnosed to recognize their true nature and to allow their correct and non-invasive treatment: surgery is indicated only when recurrences and symptoms are present. Indications for aspiration of all solitary cysts of the neck should be considered to correctly identify their nature.
Annali italiani di chirurgia 72(3):343-5. · 0.23 Impact Factor
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ABSTRACT: The correct therapeutic strategy of giant hemangiomas of the liver is debated and based on two main techniques: resection and enucleation.
We report seven consecutive typical hepatic resections for giant cavernous hemangiomas in symptomatic patients. Most frequent symptom was pain at the right hypochondrium, associated with epigastric discomfort. Hepatectomy was carried out after extraparenchymal ligation of the hilary structures and parenchymal resection was performed with kellyclasia and ligation of the intraparenchymal vessels with clips. In all cases the resection was performed after intermittent clamping of the hepatic pedicle.
Three right hepatectomies, 1 right extended hepatectomy, 1 left hepatectomy and 2 left lobectomies (segments 2 and 3) were performed. Estimated blood loss ranged from 350 to 1000 ml with a mean loss of 550 ml. No major postoperative complication and no long term sequela occurred. Two episodes of cholangitis in an old patient after emergency operation regressed under medical treatment.
Enucleation is an option when a lesion is small and superficial. In the case of large and deep hemangiomas in proximity of vascular structures, typical liver resection is a safe operation entailing lower morbidity and blood loss.
Hepato-gastroenterology 44(13):231-4. · 0.66 Impact Factor
