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Biomedical subjects

A Pinchera

Publications and source records attributed to A Pinchera.

At least 181 records · Page 10Linked to original sources
PubMed1995

Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident.

Since the Chernobyl nuclear reactor accident, a striking increase of thyroid carcinoma has been reported in children exposed to radiation in Belarus. Because of its unprecedented scale and its emotional implications, this finding has raised concern and called the attention of the scientific community to this major health problem. Although epidemiologically documented, a direct correlation between thyroid cancer and radiation exposure has not been definitely proven at the molecular level. On the assumption that ionizing radiation could cause specific and common cancer-associated genetic lesions, an analysis of oncogene activation and/or tumor suppressor gene inactivation would help to define radiation-induced thyroid carcinomas. Therefore, we have analyzed by different molecular approaches, including Southern blotting, DNA transfection assay on NIH-3T3 cells, and reverse transcription-PCR analysis, six papillary carcinomas from children living in the region of Belarus at the time of the Chernobyl nuclear accident to identify tumor-specific gene rearrangements of the proto-oncogenes RET and TRK, previously found activated in a tumor type-specific manner in papillary thyroid carcinoma. Using Southern blot analysis in four cases, we could detect specific rearranged bands indicating an oncogenic activation of RET that in three cases resulted in rearranged sequences provided by the same activating gene. Moreover, the DNA of the last three cases showed a biological activity in transforming NIH-3T3 cells after the DNA-mediated transfection assay, and the respective NIH-3T3 transfectants were found to express the oncogenic fusion transcripts. These results support the possibility that RET oncogenic activation could represent a major genetic lesion associated with thyroid carcinoma in children exposed to the Chernobyl nuclear accident.

3T3 Cells↗
PubMed1995

Mild iodine deficiency during fetal/neonatal life and neuropsychological impairment in Tuscany.

The neuropsychological performance of schoolchildren living in areas with present and past iodine deficiency in Tuscany was investigated. Children were submitted to: a) block design subtest of the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a modified version of the WISC-R coding subtest which evaluate the general neuropsychological and cognitive performance, independently from familial cultural background; b) simple reaction time (RT) session which evaluates the efficiency of the whole information processing and nervous transmission mechanisms. Neuropsychological performance was tested in 107 children living in Borgo a Mozzano, an area of mild iodine deficiency (IDA) with a median urinary iodine excretion (UIE) of 64 micrograms/L (mean +/- SD: 80.1 +/- 57). One hundred and six sex and age-matched children living in Marina di Pisa, an iodine sufficient coastal village of Tuscany (ISA) with a median UIE of 142 micrograms/L (mean +/- SD: 173 +/- 95) were used as controls. Tests for neuropsychological performance were performed in 57 children living in the village of Vagli, an area with past iodine deficiency (PIDA): 30 children born before iodine prophylaxis (Group 1), when the median UIE was 32 micrograms/L (mean +/- SD: 47 +/- 22), 27 children born after the institution of iodine prophylaxis (Group 2), when the median UIE was 109 micrograms/L (mean +/- SD: 130 +/- 73). Sex and age-matched ISA-children were used as controls for each group. RTs were significantly delayed (p < 0.05) in IDA than in ISA children, while block design and coding subtests showed no significant difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1995

Thyroid blood flow evaluation by color-flow Doppler sonography distinguishes Graves' disease from Hashimoto's thyroiditis.

Thyroid hypoechogenicity at ultrasound is a characteristic of autoimmune thyroid diseases, with an overlap of this echographic pattern in patients affected by Graves' disease or Hashimoto's thyroiditis. Aim of the present paper was to study the thyroid blood flow (TBF) by color-flow doppler (CFD) and peak systolic velocity (PSV) at the inferior thyroid artery in 37 Graves' and 45 goitrous Hashimoto's thyroiditis patients. CFD pattern was defined as normal (or type 0): TBF limited to peripheral thyroid arteries (PSV = 17.7 +/- 3 cm/sec, mean +/- SD); type I: TBF mildly increased; type II: TBF clearly increased; type III: TBF markedly increased. The CFD was in direct relationship to the PSV. Out of 18 patients with Graves' disease and untreated active hyperthyroidism CFD pattern was type III in 17 and type II in 1. The PSV was 42.1 +/- 15 cm/sec. In 17 patients euthyroid under methimazole, the CFD pattern was type 0 in 3 (17%) type I in 5 (30%), type II in 5 (30%), type III in 4 (23%). In this group of Graves' patients the PSV was 36 +/- 14 cm/sec. In two patients, hypothyroid after radioiodine treatment, the CFD pattern was type 0 in 1 and type I in 1. In the group of Hashimoto's patients TBF was in no relationship with thyroid status or treatment and was type 0 in 22 (49%), type I in 20 (44%), type II in 3 (7%), while none had type III CFD pattern. Thyroid hypoechogenicity at ultrasound was present in 32/37 (86%) Graves' and 41/45 (91%) Hashimoto's patients. All the four patients with Hashimoto's thyroiditis and normal thyroid ultrasound pattern had also a normal CFD pattern, while 4/5 patients with Graves' disease and normal echographic pattern had an increased TBF. In conclusion, a diffusely increased thyroid blood flow is pathognomonic of untreated Graves' disease and an abnormal CFD pattern identifies the majority of Graves' patients with a normal thyroid ultrasound pattern. Thus, CFD sonography may be useful in distinguishing patients with Graves' disease and Hashimoto's thyroiditis having a similar thyroid echographic pattern at ultrasound.

Diagnosis, Differential↗
PubMed1995

Early treatment of hereditary medullary thyroid carcinoma after attribution of multiple endocrine neoplasia type 2 gene carrier status by screening for ret gene mutations.

BACKGROUND: Germline missense point mutations of the ret proto-oncogene have been shown as causative in multiple endocrine neoplasia type 2 (MEN 2A and 2B) and in familial medullary thyroid carcinoma (FMTC). Most of the mutations are found in exon 10, 11, or 16 of the gene and are easily recognized by restriction analysis. METHODS: Using restriction analysis, we screened 58 subjects from nine kindreds. RESULTS: Family members (n = 16) already known to be affected with the disease carried the germline mutation. Among the 42 subjects apparently unaffected, 37 were not gene carriers and 5 were gene carriers. Basal and pentagastrin-stimulated serum calcitonin levels were normal in two patients and abnormal in three. All patients were treated with total thyroidectomy and central node dissection. In all cases multiple foci of MTC were shown at histologic examination. CONCLUSIONS: Our data indicate that genetic screening of MEN2 pedigrees allows the early identification of gene carriers. Because surgery of MTC in the preclinical phase has high probability of curing these patients, we suggest genetic screening soon after birth and total thyroidectomy in gene carriers as early as possible.

Base Sequence↗
PubMed1995

Thyroid autoimmunity and ageing.

Ageing is associated with the appearance of several serum autoantibodies, including thyroid autoantibodies. The biological and clinical significance of this phenomenon is still unknown, since, with the exception of primary myxedema, the prevalence of clinically overt thyroid autoimmune diseases is not increased in the elderly. The peculiar link between autoimmune thyroid failure and ageing is also underscored by the high prevalence of subclinical hypothyroidism in elderly subjects with positive serum thyroid autoantibodies, and could be the consequence of preferential age-dependent expression of destructive effector mechanisms and/or increased target gland susceptibility. Thyroid autoimmunity and subclinical hypothyroidism have also been implicated in the pathogenesis of other age-associated disorders, in particular coronary heart disease. Interestingly, recent data from our laboratories showed that thyroid autoantibodies are rare in healthy centenarians and in other highly selected aged populations, while they are frequently observed in unselected or hospitalized elderly. Taken together, these data suggest that thyroid autoimmune phenomena are not the consequence of the ageing process itself, but rather might be related to age-associated disease.

Aging↗
PubMed1995

Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal?

Measurement of thyroglobulin (Tg) in serum with anti-Tg autoantibodies (TgAb) represents a difficult challenge. Immunoradiometric assays (IRMA) employing monoclonal anti-Tg antibodies not cross-reacting with endogenous TgAb have recently been developed and proposed for Tg assays in TgAb-positive sera. The aim of the present investigation was to assess the clinical reliability of this approach. Assays of serum Tg in patients with and without TgAb using one such monoclonal antibody IRMA (Thyroglobulin IRMA-Pasteur; IRMA-1) were compared with those obtained by a conventional IRMA employing polyclonal anti-Tg antibodies (HTGK-Sorin; IRMA-2). Preliminary studies for assessment of the interference of TgAb showed that the recovery of added Tg was significantly higher (P < 0.01) when determined by IRMA-1 (64.6 +/- 23%) than by IRMA-2 (49.5 +/- 20%). Study groups included 79 patients with differentiated thyroid carcinoma (DTC) treated by total thyroidectomy and radioiodine ablation; 24 had no metastases or residual thyroid tissue, 31 had a thyroid residue, and 24 had metastatic disease. Seventy-five patients with autoimmune thyroid disease (47 with Graves' and 28 with Hashimoto's disease) were also included. In TgAb-negative sera from DTC patients, similar Tg concentrations were found by both IRMA, i.e. undetectable in most patients with no residual thyroid or neoplastic tissue, low to moderately elevated in the majority of those with residual thyroid tissue, and markedly elevated in all patients with metastatic disease. Serum Tg was undetectable by both assays in several TgAb-positive sera from DTC patients with residual thyroid tissue or metastatic disease, respectively, in whom a detectable or even high serum Tg concentration was expected. Despite the lower in vitro interference of TgAb in IRMA-1, there was no difference between the two assays. In the group of patients with thyroid autoimmune disease, serum Tg concentrations were found to be high in TgAb-negative sera and much lower in TgAb-positive sera by both IRMAs. In conclusion, the present study demonstrates that the use of a monoclonal antibody IRMA for serum Tg, although less susceptible to in vitro TgAb interference, does not necessarily provide any substantial advantage with respect to a conventional polyclonal IRMA in detecting Tg in TgAb-positive sera. The finding of undetectable or lower than expected serum Tg by either method in TgAb-positive serum may well reflect a truly reduced serum Tg concentration. This might be due to an accelerated Tg metabolic clearance in the presence of TgAb.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Identification of the Cys634-->Tyr mutation of the RET proto-oncogene in a pedigree with multiple endocrine neoplasia type 2A and localized cutaneous lichen amyloidosis.

Following the recent identification of specific germline mutations of the RET proto-oncogene in Multiple Endocrine Neoplasia type 2A (MEN2A) patients, we looked for mutations of this gene in a pedigree showing recurrence of MEN2A and localized Cutaneous Lichen Amyloidosis (CLA). Basal calcitonin and/or pentagastrin test performed in all the 10 available members of this pedigree confirmed the clinical diagnosis and allowed the presymptomatic identification of an additional carrier. A cys634-->tyr missense mutation, already reported as causative in MEN2A patients, was identified after SSCP analysis and direct sequencing of exon 11 of the RET protooncogene in one individual affected with both MEN2A and CLA, thus suggesting a common etiology for the two disorders. Taking advantage of the observation of an RsaI restriction site in the sequence surrounding the mutated codon, we could demonstrate that the same mutation is present in three other affected members, in the presymptomatic carrier and in one additional 25 years old healthy member who shows a mildly positive pentagastrin test.

Amyloidosis↗
PubMed1994

Detection of antibodies blocking thyrotropin effect using Chinese hamster ovary cells transfected with the cloned human TSH receptor.

Chinese hamster ovary (CHO) cells transfected with the cloned human TSH receptor (CHO-R) were used to develop an assay to detect thyroid autoantibodies blocking the TSH-dependent cAMP production (TSHBAb). The study group included 38 patients with goitrous Hashimoto's thyroiditis (HT) and 47 subjects with atrophic thyroiditis (AT). In the HT group, 8 patients had subclinical hypothyroidism (HT-SH) and 30 had overt hypothyroidism (HT-H). Thirty normal subjects served as controls. Immunoglobulin G (IgG) was prepared from serum by double chromatography on DEAE-Sephadex. CHO-R cells were seeded in 96-well plates and were cultured for 48 h before the assay in RPMI-1640 medium plus 1 mmol/L glutamine, 10% fetal calf serum, and 0.4 g/L geneticin. In the assay for TSHBAb, CHO-R cells were incubated with IgG alone (0.5-2 mg/ml), TSH alone (0.2-625 mU/L), or IgG plus TSH; all samples were diluted in hypotonic medium containing 0.5 mmol/L isobutylmethylxanthine (IBMX). After 2 h of incubation at 37 degrees C in 5% CO2-95% air atmosphere, TSH-stimulation was quantified by measuring extracellular cAMP by a RIA. IgGs from normal subjects did not significantly modify the stimulation of adenylate cyclase produced by TSH, the results obtained ranging between -30% and +18% (mean +/- SD = -3 +/- 14%). All IgGs producing an inhibition greater than 2SD from the mean of controls (> 25%) were considered positive for blocking antibodies. TSHABAb were detected in 1/8 (12.5%) patients with HT-SH, in 7/30 (23.3%) with HT-H and 16/47 (34.0%) patients with AT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Serum soluble interleukin 2 (IL-2) receptor (sIL-2R) in differentiated thyroid carcinoma.

Increased concentrations of serum soluble interleukin-2 (IL-2) receptor (sIL-2R), a marker of T-lymphocyte activation, have been found in several metastatic solid tumors. To our knowledge, no information is available on serum sIL-2R in differentiated thyroid carcinoma (DTC). Aim of this study was to evaluate whether disease activity and/or thyroid status may affect circulating sIL-2R in DTC, since it is has recently been demonstrated that serum thyroid hormone concentration positively modulates circulating sIL-2R. DTC patients were divided into 3 groups: Group A: 48 patients without metastases or local recurrences; Group B: 16 patients with cervical lymph node metastases; Group C: 22 patients with distant metastases. All patients were evaluated after total thyroidectomy both off and on L-thyroxine (L-T4) therapy. Control group was composed by 20 healthy euthyroid subjects. sIL-2R was assayed by solid-phase ELISA. In the hypothyroid state, sIL-2R levels of Group A were significantly lower when compared to normal controls (256 +/- 130 vs. 461 +/- 186 U/ml, p < 0.001 by Student t test); Group B and Group C patients off L-T4 therapy had sIL-2R concentrations significantly higher (479 +/- 407 U/ml, Group B; 519 +/- 746 U/ml, Group C) when compared to hypothyroid patients of Group A (p < 0.01 and p < 0.05, respectively), but not significantly different from normal euthyroid controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular↗
PubMed1994

Expression of p21 ras protein as a prognostic factor in papillary thyroid cancer.

We studied the expression of p21, the ras encoded protein, in primary tumour of 45 patients with papillary thyroid cancer (PTC). Patients were grouped according to outcome so that one group (31 patients) had a good outcome and the other (14 patients) a fatal outcome, after a follow-up of at least 5 years. The presence of p21 ras protein was assessed by immunohistochemistry with a specific monoclonal antibody (MAb Y-13259). The results were correlated with the outcome, with the expression of proliferating cell nuclear antigen (PCNA)/cyclin (as a marker of cell proliferation) and with other well established prognostic factors for PTC (age, grading, extension and tumour size; Endocrinol Metab Clin North Am 1990, 19, 545-576). p21 staining in tumours of living patients was negative in 15, weakly positive (1+) in 10 and strongly positive (2+ or more) in 6 patients. In tumours from deceased patients, p21 staining was negative in 1, weakly positive in 2 and strongly positive in the remaining 11 patients (P < 0.001, chi 2). PCNA immunostaining was increased in 63.6% (7/11) of the tumours from deceased patients compared to 17.8% (5/28) of the tumours of living patients, but no direct correlation was found between p21 and PCNA expression. Among the other prognostic factors studied, only age > or = 40 years was a significant predictor of poor outcome. The survival curve of patients with strongly positive p21 staining was similar to that of patients aged > or = 40 years at the time of diagnosis. The combination of p21 > or = 2+ and age > or = 40 was superior to age alone (P < 0.05) as a prognostic indicator of poor outcome. In conclusion, our results indicate that the p21 product of the ras (proto)oncogene is differently expressed in PTC, in relation to the degree of aggressiveness. Regardless of the pathogenetic role of the ras oncogene in thyroid tumorigenesis, our data indicate that the expression of the p21 ras protein may be regarded as a prognostic indicator in PTC. Furthermore, overexpression of p21 ras protein is associated with patients in the older age groups, and might contribute to the poor prognosis of elderly patients.

Adolescent↗