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S Benvenga

Publications and source records attributed to S Benvenga.

At least 19 recordsLinked to original sources
PubMed2006

In silico identification of potential new latex allergens.

BACKGROUND: Allergy to latex of Hevea brasiliensis is a frequent problem. In spite of the significant progress of research, the identity and cross-reactivity of some latex allergens are unknown. OBJECTIVE: To identify, among the fully characterized latex proteins, those with a higher probability to be allergenic. METHODS: We used in silico techniques (amino acid sequence comparison and molecular modelling) to identify potential new allergens among the known proteins of H. brasiliensis. RESULTS: Cu/Zn superoxide dismutase, heat shock protein and calmodulin of H. brasiliensis show highly significant (E < 10(-9)) amino acid sequence homologies with known allergens. CONCLUSION: On the basis of our data, Cu/Zn superoxide dismutase, heat shock protein and calmodulin are the most probable allergens among fully characterized proteins of H. brasiliensis, and could potentially explain, at least in part, the multiple cross-reactivities of latex with vegetable foods and other plant-derived products. Consequently, we think that the above proteins should be particularly considered in the future laboratory and clinical research.

Allergens↗
PubMed2006

Immunoexpression of the CD30 ligand/CD30 and IL-6/IL-6R signals in thyroid autoimmune diseases.

To elucidate the role of Th2 cytokines in autoimmune thyroid diseases, we have studied by immunohistochemistry the expression of two Th2 ligand/receptor systems (CD30-L/CD30 and IL-6/IL-6R) in goitrous Graves' disease (GD) and Hashimoto's thyroiditis (HT). A total number of 50 nodular goiters (NG), including 10 GD showing a lymphoid aggregate grade I, 30 HT 8 of which had a lymphoid aggregate of grade I, 12 of grade II and 10 grade III, and 10 colloid goiters have been evaluated. In addition, 5 normal thyroids were included in the study as controls. Reactivity of ligand and cognate receptor of both CD30-L/CD30 and IL-6/IL-6R pathways was observed in a greater proportion of GD, compared to HT (P<0.005). In HT, the expression of CD30-L/CD30 system was detected more frequently than IL-6/IL-6R (P<0.05) and showed an inverse correlation with the grade of lymphoid aggregate, whereas IL-6/IL-6R correlated positively with lymphocyte infiltration (P<0.05). Based on our results concerning a dominance of Th2 cytokines in GD, we postulate that CD30-L/CD30 and IL-6/IL-6R systems could play a major role in the pathogenesis of GD. However, the expression of CD30L/CD30 and IL-6/IL-6R in HT suggests that Th2 mechanisms are involved also in tissue damage of HT. The two systems could contribute to drive the autoimmune response skewing toward a Th2 phenotype and this appears to be correlated with the lymphoid aggregate grade.

Adult↗
PubMed2005

Effects of L-carnitine on thyroid hormone metabolism and on physical exercise tolerance.

L-carnitine (CARN) is a water-soluble, naturally occurring quaternary amine ubiquitous in biological fluids and animal tissues; in these tissues, CARN plays an important role in energy metabolism. Skeletal muscles store about 95 % of a total of 20 g CARN contained in the adult human body, but high-intensity physical exercise decreases the CARN muscle content. The daily allowance of CARN is mainly satisfied by diet. Keeping in mind important interstudy differences, the general conclusion is that CARN supplementation may enhance athletic performance when coupled to physical exercise itself. Healthy, essentially sedentary persons and untrained individuals do not benefit from supplementation, and certainly not if CARN is administered for a few days. CARN was also shown to modulate thyroid hormone action in peripheral tissues, the most frequent modulation observed being inhibition.

Animals↗
PubMed2005

Molecular analysis of the PDS gene in a nonconsanguineous Sicilian family with Pendred's syndrome.

OBJECTIVE: The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the Pendred's syndrome (PDS) gene that encodes pendrin, a chloride/iodide transporter expressed in the thyroid, the inner ear, and the kidney. In this study we performed clinical and molecular analyses in three siblings from a nonconsanguineous Sicilian family who presented with the clinical features of Pendred's syndrome. PATIENTS AND MOLECULAR ANALYSES: In two sisters and one brother, the clinical diagnosis of Pendred's syndrome was established based on the findings of sensorineural hearing loss and large goiters. Thyroid function tests, perchlorate discharge tests, thyroid ultrasound, and scintigraphy were performed in all affected individuals. Exons 2 to 21 of the PDS gene were amplified by polymerase chain reaction (PCR) and both strands were submitted to direct sequence analysis. RESULTS: The clinical diagnosis of Pendred's syndrome was supported by a positive perchlorate discharge test in the three afflicted siblings. Direct sequence analysis of the PDS gene revealed that all three harbored one allele with a novel mutation 890delC leading to a frameshift mutation and premature stop codon at position 302 (FS297 > 302X). On the other allele, two of the siblings had a previously described transition 1226G > A, which results in the substitution of arginine by histidine at position 409 (R409H). In the index patient, no mutation could be identified on the other allele. In functional studies, these mutants lose the ability of pendrin to mediate iodide efflux. CONCLUSIONS: All three patients included in this study presented with the classic Pendred syndrome triad. Two siblings were compound heterozygous for mutations in the coding region of the PDS gene. The third individual could have an unidentified mutation in a regulatory or intronic region of the PDS gene, or an identical phenotype caused by distinct pathogenic mechanisms.

Adolescent↗
PubMed2005

Central hormonal regulation and dimorphism of arousal.

From studies in animals, we have learned that differences in sexual behaviour between males and females reflect anatomical and biochemical differences between the male and female brain. A masculine behaviour (and therefore a masculine brain) results from the biological effect on the developing brain exerted by testosterone, which is secreted by the gonads and aromatized into oestrogens in the brain. However, congenital disorders of the androgen as well as oestrogen signalling in human males have failed to show any appreciable derangement in sexual behaviour. Based on other evidence in animals, sexual differences in brain (and behaviour) are not hormonally triggered but genetically determined. This other theory states that sexual behaviour is determined by the chromosomal sex existing in cells, including brain cells. A number of excitatory and inhibitory signals modulate the activity of certain brain structures. Scientists have begun to test some of these chemicals or their synthetic analogues/antagonists in humans.

Animals↗
PubMed2005

Disappearance of a virilizing adrenal tumor following therapy with cyproterone acetate.

A 57-year-old woman presented with an apparently obvious diagnosis of iatrogenic virilization. At the age of 51, she began a 4-year treatment with prednisone or cyclosporine, which are known to promote hair growth, for Behçet disease. At the age of 56, osteoporosis was overtreated with the anabolic steroid nandrolone. Insignificant inhibition by dexamethasone of the extremely high serum concentrations of testosterone and less high concentrations of weak androgens prompted us to search for a virilizing tumor. Computed tomography showed a 2.3 x 1.5 cm nodule in the right adrenal gland. As the patient refused surgery, virilization was treated with the antiandrogen cyproterone acetate (CPA), but for only 4 months because clinical and hormone abnormalities reversed and the tumor was no longer visible. The patient remains symptom-free. This first report of a curative effect of CPA on a purely virilizing adrenal tumor opens new avenues in the management of such tumors.

Adrenal Gland Neoplasms↗
PubMed2004

Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI).

In adults, hypopituitarism and growth hormone deficiency (GHD) should be suspected and diagnosed within an appropriate clinical context. It has been demonstrated that all patients with primary hypothalamic-pituitary diseases before and after any medical intervention (defined as neurosurgery, radiotherapy and medical therapy) are at obvious risk - more than just at high risk - for hypopituitarism (greater than 80% had severe GHD). The same obvious risk applies to patients diagnosed as having congenital or acquired GHD in childhood (between 30% and 50% of patients with severe GHD after retesting). Taking into account the fragility of the infundibular-hypothalamic structure, patients with other common pathological conditions of the central nervous system (CNS), such as traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) or primary brain tumours (BT) with related medical intervention could be at risk for developing hypopituitarism, including GHD. GHD is the first and most common sign of pituitary impairment. Despite the risk of pituitary dysfunction and the results of some studies that these risks are greater than previously believed, neuroendocrine evaluations are still not routinely included as part of the clinical management plan for patients with TBI and SAH. Preliminary results of a multicenter study performed under the auspices of the Italian Society of Endocrinology underscore the high risk of hypopituitarism and GHD under these clinical conditions. Thus, careful screening of pituitary function should always be performed in patients following TBI and SAH.

Brain Injuries↗
PubMed2003

Distinctive expression of STAT3 in papillary thyroid carcinomas and a subset of follicular adenomas.

Hepatocyte growth factor (HGF), HGF receptor (c-met) and the interleukin 6 (IL-6) are expressed in thyroid nodules. In extra-thyroidal tissues, the HGF/c-met and IL-6/IL-6 receptor (IL-6R) systems activate STAT3, a member of the signal transducers and activators of transcription (STATs) family. To evaluate whether either system utilizes STAT3 in thyroid nodules, we examined the immunohistochemical expression of HGF, c-met, IL-6, IL-6R, STAT3 in 6 normal thyroids and in 68 thyroid nodules. STAT3 expression was observed in 12/12 (100%) papillary thyroid carcinomas (PTC) but in none of the follicular tumors. Among benign thyroid nodules, only 2/10 (20%) follicular adenomas (FA) were STAT3+. All these 14 STAT3+ cases expressed both HGF and c-met, but only 5 PTC co-expressed IL-6 and IL-6R and the 2 FA were IL-6+ but IL-6R-. The remaining 8 FA were all HGF/c-met-, but IL-6+; of these 8, only 2 were also IL-6R+. In conclusion, in thyroid nodules STAT3 is expressed only in PTC and a number of FA. Since these cases are consistently HGF+/c-met+ and only one-third of them co-express IL-6/IL-6R, STAT3 expression correlates with the HGF/c-met expression, not with the IL-6/IL-6R expression. The 100% rate of expression of the HGF/c-met/STAT3 signaling in PTC could be relevant for the establishment of the papillary phenotype. Because of the communeness of a HGF/c-met/STAT3 pattern between all PTC and a subset of FA, we speculate that a fraction of FA may progress to PTC.

Adenoma↗
PubMed2002

Thyroxine binding to members and non-members of the serine protease inhibitor family.

Partition of T4 to plasma proteins is classically attributed only to TBGC approximately/= 70%), transthyretin (approximately/= 15%) and albumin (approximately/= 10%), based on zone electrophoresis. Since TBG migration spans the alpha1 and alpha2 regions, and since HDL, which have alpha1 migration, transport approximately/= 4% of circulating T4, other alpha-globulins could bind T4 and "contaminate" the TBG area. Hence, we determined the association of [125I]T4 to TBG and, for comparison, to transthyretin and albumin. Sera from 50 normolipidemic individuals were equilibrated with [125I] T4 and analyzed by both zone electrophoresis and radioimmunoprecipitation with specific antisera. Transthyretin-T4 or albumin-T4 bindings as assessed by the two methods agreed, while TBG-T4 did not, because other alpha-globulins carrying T4 with low affinity co-migrated with TBG. Some, but not all, of these alpha-globulins belong to the same superfamily of TBG and also bind steroid hormones.

Adult↗
PubMed2002

Thyroid hormone autoantibodies in primary Sjögren syndrome and rheumatoid arthritis are more prevalent than in autoimmune thyroid disease, becoming progressively more frequent in these diseases.

To verify the greater prevalence of circulating thyroid hormone autoantibodies (THAb) in primary Sjogren syndrome (SS) vs Hashimoto's thyroiditis (HT) and Graves' disease (GD), we measured THAb in the serum of patients with these 3 diseases who were sampled from 1998-1999 (no.=20, 88, 25) and 1990-1992 (no.=13, 75, 31). Patients with rheumatoid arthritis (RA) (no.=23 and 16) and other collagenoses (no.=20 and 16) were also studied. A third series of patients with these 5 diseases was studied from 1975-1982, and data have been taken into account. THAb were detected using a specific radioimmunoprecipitation method, and their presence was correlated with the presence of TG antibodies (TGAb). We found that IgG antibodies against T3, T4 or both were present with these prevalences in the 1975-1982, 1990-1992 and 1998-1999 series: HT=1, 4, 20%; GD=2, 6, 32%; SS=20, 31, 50%; RA=0, 12, 26%; other collagenoses=0, 0, 0%. The majority of the Sjogren or arthritis cases positive for THAb were negative for TGAb, while the opposite was true for the 2 autoimmune thyroid diseases. We conclude that prevalence of THAb in the 2 non-thyroid autoimmune diseases is greater than in the 2 thyroid autoimmune diseases. In addition, prevalence of THAb is increasing over time regardless of disease. Molecular similarity between extra-thyroid connective proteins (specifically associated to primary SS and RA) and iodinated regions of TG, and an increased preponderance of environmental factors as triggers of autoimmune diseases might account for our findings.

Adult↗
PubMed2002

Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor.

Data on the expression of interleukin 6 (IL-6)/interleukin 6 receptor (IL-6R) in thyroid nodules is scarce. Based on our recent data of CD30 ligand (CD30L)/CD30 receptor (CD30) in these nodules and on the knowledge that this signal stimulates IL-6 production in non-thyroid neoplasms, we wanted to evaluate the immunocytochemical expression of these 2 ligand/receptor systems in a large archival series of paraffin-embedded specimens. These specimens included 6 normal thyroids and 130 thyroid nodules. Co-expression of IL-6 and IL-6R in the epithelial (follicular) cells was observed solely in CD30L/CD30 positive nodules: 5/15 (33%) oncocytic adenomas; 6/30 (20%) follicular adenomas which belonged to 2 variants (4/4 microfollicular toxic and 2/2 hyalinizing trabecular); 9/30 (30%) papillary thyroid cancers (PTC), all belonging to the conventional variant. In PTC the proportion of tumor epithelial cells that were IL6 positive was inversely correlated with the pTNM staging (r=-0.549, p=0.01). All 15 follicular cancers (FTC), all 6 anaplastic cancers (ATC) were IL-6/lL-6R negative; 14/15 FTC and 5/6 ATC were CD30L/CD30 negative. In another oncocytic adenoma, another 4 conventional PTC and another 7 non-conventional PTC CD30L/CD30 expression was associated to expression of IL-6 only. IL-6 staining associated to absent expression of CD30L and CD30 was observed in 7 follicular adenomas (all belonging to variants different from toxic and hyalinizing trabecular), 2 oncocytic adenomas, 5 of the 30 colloid nodules and 2 normal thyroids. Of the 6 tumors arising from the parafollicular C cells (medullary thyroid cancer, MTC), all 3 that had metastasized were CD30L/CD30/IL-6 positive and IL-6R negative; only IL-6 expression was lost in both the local and distant metastases. This finding matched the loss of IL-6 expression in one PTC metastasis. All 3 non-metastasized MTC were IL-6/IL-6R negative, and 1/3 was CD30L positive/CD30 negative. We conclude that only in a subset of both benign and malignant thyroid nodules the IL-6/IL-6R signal could be induced by the CD30L/CD30. IL-6 expression is related with aggressiveness in both PTC and MTC. In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30.

Adenocarcinoma, Follicular↗
PubMed2002

Heterogeneity of the thyroglobulin epitopes associated with circulating thyroid hormone autoantibodies in hashimoto's thyroiditis and non-autoimmune thyroid diseases.

We previously implicated TG leakage from fine-needle aspiration biopsy (FNAB) as responsible for circulating thyroid hormone autoantibodies (THAb). However, THAb were not always associated with TGAb. In the literature these negative findings have been interpreted against a role of TG as the antigen for THAb. To evaluate the TGAb status more fully and to gain information on TG epitopes involved in THAb development, we measured: 1) TGAb with an independent hemagglutination assay (HA), and 2) epitope specificity in a competitive ELISA using 2 monoclonal Abs (mAb) against TG: mAb 42C3 and mAb 134C2. MAb 42C3 recognizes a cross-reactive iodinated epitope, whereas 134C2 is specific for human TG. We tested 12 Hashimoto's thyroiditis (HT) and 35 non-HT patients sampled prior to, 1 and 3 months after FNAB. We found that, irrespective of thyroid disease or post-FNAB THAb status, certain patients previously classified as TGAb negative by IRMA tested TGAb positive by HA or by competition ELISA and vice versa. A post FNAB positive response to the 42C3 iodinated epitope in only one THAb IgM-T4+ve HT and a few THAb negative non-HT patients was observed. Furthermore, we observed that the 3 non-HT patients who expressed IgM-T3 THAb failed to bind either TG-mAb epitope. We conclude that a single TGAb assay is not sufficient to define the TGAb status, which can be achieved reliably only by using multiple TGAb assays. In addition, the TG-iodinated epitope recognized by 42C3 is not a major epitope in post-FNAB THAb, and the T3-epitope involved in THAb remains distinct from the mAb epitopes. In light of recent data in the literature, we further suggest that the responsible epitopes are more likely to be expressed in leaked TG fragments, rather than leaked intact TG.

Antibodies, Monoclonal↗
PubMed2002

Sexual inactivity results in reversible reduction of LH bioavailability.

We have recently documented significantly reduced serum testosterone (T) levels in patients with erectile dysfunction (ED). To understand the mechanism of this hypotestosteronemia, which was independent of the etiology of ED, and its reversibility only in patients in whom a variety of nonhormonal therapies restored sexual activity, we measured serum luteinizing hormone (LH) in the same cohort of ED patients (n=83; 70% organic, 30% nonorganic). Both immunoreactive LH (I-LH) and bioactive LH (B-LH) were measured at entry and 3 months after therapy. Based on outcome (ie number of successful attempts of intercourse per month), patients were categorized as full responders (namely, at least eight attempts; n=51), partial responders (at least one attempt; n=20) and non-responders (n=16). Compared to 30 healthy men with no ED, baseline B-LH (mean+/-s.d.) in the 83 patients was decreased (13.6+/-5.5 vs 31.7+/-6.9 IU/L, P<0.001), in the face of a slightly increased, but in the normal range, I-LH (5.3+/-1.8 vs 3.4+/-0.9 IU/L, P<0.001); consequently, the B/I LH ratio was decreased (3.6+/-3.9 vs 9.7+/-3.3, P<0.001). Similar to our previous observation for serum T, the three outcome groups did not differ significantly for any of these three parameters at baseline. However, outcome groups differed after therapy. Bioactivity of LH increased markedly in full responders (pre-therapy=13.7+/-5.3, post-therapy=22.6+/-5.4, P<0.001), modestly in partial responders (14.8+/-6.9 vs 17.2+/-7.0, P<0.05) but remained unchanged in non-responders (11.2+/-2.2 vs 12.2+/-5.1). The corresponding changes went in the opposite direction for I-LH (5.2+/-1.7 vs 2.6+/-5.4, P<0.001; 5.4+/-2.2 vs 4.0+/-1.7, P<0.05; 5.6+/-1.2 vs 5.0+/-1.2, respectively), and in the same direction as B-LH for the B/I ratio (3.7+/-4.1 vs 11.8+/-7.8, P<0.001; 4.2+/-4.3 vs 5.8+/-4.2, P<0.05; 2.1+/-0.7 vs 2.6+/-1.3, respectively). We hypothesize that the hypotestosteronemia of ED patients is due to impaired bioactivity of LH. This reduced bioactivity is reversible, provided that resumption of sexual activity is achieved regardless of the therapeutic modality. Because biopotency of pituitary hormones is controlled by the hypothalamus, LH hypoactivity should be due to the hypothalamic functional damage associated to the psychological disturbances which unavoidably follow sexual inactivity.

Adult↗
PubMed2002

Immunoexpression of the hepatocyte growth factor (HGF), HGF-receptor (c-met) and STAT3 on placental tissues from malformed fetuses.

To characterize the possible relationship between the expression of the HGF/HGF-R system with transcription factor STAT3, responsible for morphogenetic response of HGF stimulation, and the embryonic development alterations, we investigated, by immunohistochemistry, the expression of HGF, c-met and STAT3 in 9 placentas from malformed fetuses and 9 control placentas from non-malformed fetuses. The major and distinct patterns of expression characterizing the placentas from malformed fetuses were a higher percentage mean of stromal cells stained for HGF, c-met and STAT3 antibodies (60%, 66% and 54%, respectively on fibroblast cells and 44%, 57% and 42%, respectively on myofibroblast cells) and a lower percentage mean of cytotrophoblast cells stained for the same antibodies (2%, 2% and 1%, respectively), than in control placentas. In fact, in this latter group, the stromal fibroblast cells were stained in a percentage mean of 27%, 22% and 7%, respectively; the stromal myofibroblast cells in a percentage mean of 5%, 6% and 2%, respectively and the cytotrophoblast cells in a percentage mean of 25%, 34% and 18%, respectively. The expression of each antibody on stromal cells in both groups suggests an alternative role of the HGF/HGF-R system activating the via STAT3 transdution and operating on placental tissues, overall in organogenesis alteration conditions. This immunohistochemical approach could be used in the diagnostic practice of pathologists on chorionic villi biopsy when genetic alterations are absent and ultrasound aspects are doubtful for malformations.

DNA-Binding Proteins↗
PubMed2001

Re-evaluation of the thyroxine binding to human plasma lipoproteins using three techniques.

Using gel filtration chromatography (GFC), we found that human VLDL, LDL and HDL transport approximately 0.03, 0.2 and 3% of plasma T4. As T4 could dissociate from carriers during GFC, we evaluated [125I]T4 transport to lipoproteins (Lp) in 50 normolipidemic and euthyroid subjects by GFC and 2 independent methods: zone electrophoresis (ZE) and radioimmunoprecipitation (RIP). At GFC, VLDL+LDL transported less T4 (approximately 0.3%) than either ZE (approximately 1.3%) or RIP (approximately 1.5-2.0%). In contrast, GFC values for the HDL (approximately 3%) were close to the RIP values (approximately 3.5%), but lower than ZE (approximately 8.5%) because of partial co-migration with TBG. In conclusion, GFC underestimates T4 binding to VLDL and LDL, which, indeed, is of the same magnitude as binding of some steroid hormones to CBG and SHBG. Hence, the anti-atherosclerotic effects of T4 resulting from binding to the LDL should be greater than anticipated based on GFC data.

Adult↗
PubMed2001

Expression of CD30 ligand and CD30 receptor in normal thyroid and benign and malignant thyroid nodules.

Because the CD30 ligand (CD30L)/CD30 receptor (CD30) system is expressed in certain malignancies, but has not been studied in thyroid nodules, we investigated its immunohistochemical expression in 6 normal thyroids (NT) and 131 thyroid nodules: 28 colloid nodules (CN), 45 adenomas (15 oncocytic [OA], 30 follicular [FA]) and 58 carcinomas (15 follicular [FTC], 1 insular [ITC], 6 anaplastic [ATC], 30 papillary [PTC], and 6 medullary [MTC]). NT and CN expressed neither CD30L nor CD30 (CD30L-/CD30-). Forty percent of OA and 20% of FA showed epithelial coexpression of CD30L and CD30, and interstitial expression of CD30L, which was also observed in the surrounding normal tissue. Within malignancies, epithelial coexpression of CD30L and CD30 was observed in 7% of FTC, 33% of ATC, 67% of PTC, and 67% of MTC. Only PTC and MTC showed epithelial expression of CD30L in the perinodular tissue with similar frequency (80% PTC, 75% MTC). PTC and MTC had the highest proportion of CD30L+ or CD30+ cells, and together with OA, a thus far unreported nuclear location of CD30L. In PTC, the proportion of CD30L+ cells and the prevalence of nuclear location of CD30L correlated inversely and directly, respectively, with aggressiveness. In conclusion, CD30L/CD30 signaling is activated only past the colloid nodule stage, most frequently in an autocrine fashion.

CD30 Ligand↗