PubMed Health⌕ Search

Biomedical subjects

F Santini

Publications and source records attributed to F Santini.

At least 127 records · Page 7Linked to original sources
PubMed1989

Thyroid autoantigens and their relevance in the pathogenesis of thyroid autoimmunity.

Humoral and cellular immune responses are both involved in autoimmune disorders of the thyroid gland. In the last five years, new substantial data have been obtained on the nature and the expression of thyroid cell surface autoantigens and on the demonstration of the functional heterogeneity of autoantibodies to the thyroid stimulating hormone (TSH) receptor. In the present report, attention will be mainly focused on recent studies carried out in our laboratory. The main autoantigens so far identified include the 'microsomal' antigen, thyroglobulin and the TSH receptor. For many years the 'microsomal' antigen (M) was considered a poorly characterized constituent of the cytoplasm of the thyroid cell. In the last five years, several lines of evidence were provided indicating that M is also well represented on the surface of the follicular cell and is identical to thyroid peroxidase (TPO). The use of anti-TPO monoclonal antibodies, presently available, have confirmed this antigenic identity. Microsomal (anti-TPO) antibodies are very useful markers of autoimmune thyroid disorders and are generally present in Hashimoto's thyroiditis, idiopathic myxedema and Graves' disease. TSH receptor antibodies (TRAb) are present in the sera of patients with Graves' disease. TRAb are able to stimulate thyroid adenylate cyclase and also to mimic TSH in its thyroid growth stimulation. Thus, these antibodies may have a pathogenetic role in goiter formation and in thyroid hyperfunction in Graves' disease. TRAb were also shown to inhibit both TSH binding to its receptor and TSH-stimulated adenylate cyclase activity. Recently TRAb, which inhibited TSH-stimulated adenylate cyclase activity, were found in idiopathic myxedema patients and may be responsible for impairment of thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantigens↗
PubMed1989

Simultaneous assay of thyroid adenylate cyclase- and growth-stimulating antibodies using FRTL-5 cells. Evidence suggesting their identity in patients with Graves' disease.

The relationship between thyroid growth-stimulating antibodies (TGSAb) and thyroid adenylate cyclase-stimulating antibodies (TSAb) in patients with Graves' disease is still a matter of controversy. To investigate this problem, we have developed an assay for the simultaneous measurement of TSAb and TGSAb using FRTL-5 cells. TSAb was detected by its ability to stimulate iodide (I-) uptake and TGSAb by the 3H-thymidine ([3H]-Tdr) incorporation assay. Thirty-four immunoglobulin G (IgG) preparations from patients with active Graves' disease were selected from a previous series in order to include both TSAb-negative IgGs (n = 9) and TSAb-positive IgGs (n = 25) by the cAMP stimulation assay, with a wide range of stimulatory activity. With one exception, the TSAb-positive IgGs produced a significant stimulation of I- uptake; 20 of them were also TGSAb-positive. The nine IgGs negative in the cAMP assay, were also negative in the I-uptake and the [3H]-Tdr incorporation assays. The majority of samples had a similar potency in the two assays and a significant positive correlation was found (r = 0.76; P less than 0.001). Two IgGs previously shown to inhibit TSH-stimulated adenylate cyclase in FRTL-5 cells produced an almost complete inhibition (80-90%) of both TSH- and Graves' IgG-stimulated I- uptake and [3H]-Tdr incorporation. In conclusion, using a simultaneous assay for thyroid growth and adenylate cyclase stimulation, TGSAb in Graves' patients were found only in TSAb-positive IgGs; both Graves' IgG-stimulated activities were inhibited by antibodies blocking the TSH-dependent adenylate cyclase stimulation. Our data strongly suggest that the same antibody may be responsible for both goitre and thyroid hyperfunction of Graves' disease.

Adenylyl Cyclases↗
PubMed1989

Antibodies to human thyroid peroxidase in autoimmune thyroid disease: studies with a cloned recombinant complementary deoxyribonucleic acid epitope.

Previous studies carried out by screening a lambda gt11 human thyroid cDNA library with serum samples from selected patients with Hashimoto's thyroiditis and a polyclonal antibody to porcine thyroid peroxidase (TPO) confirmed, at the molecular level, that TPO is a major component of the thyroid microsomal antigen (M). That investigation led to the isolation of a clone (C2) which encodes an 85-amino acid segment of TPO and harbors a major epitope recognized by serum from several patients with autoimmune thyroid disease that contained anti-M autoantibodies (MAb). In this study, C2 antigen that was produced as a beta-galactosidase fusion protein was used to establish an enzyme-linked immunoabsorbent assay for the detection of anti-C2 autoantibodies (C2Ab). C2Ab then were assayed in 191 patients with different autoimmune and nonautoimmune thyroid disorders, and 50 patients with nonthyroidal autoimmune diseases. The results were compared with the titers of anti-TPO antibodies (TPOAb; as detected by monoclonal antibody-assisted RIA) and MAb (as detected by passive hemagglutination). Positive C2Ab was found in the serum of 85 of 136 (63%) patients whose serum contained TPOAb and/or MAb. A significant positive correlation was found between the levels of C2Ab and those of TPOAb (r = 0.76; P less than 0.001) or MAb (r = 0.69; P less than 0.001), which was independent of the type of underlying autoimmune thyroid disorder. Low levels of C2Ab also were found in 10 of 105 (9%) serum samples that did not contain TPOAb. Western blot analysis carried out on the latter samples showed that in 2 samples the apparent C2Ab reactivity was due to the presence of antibodies reacting with beta-galactosidase. In conclusion, we confirmed the validity of screening lambda gt11 cDNA human thyroid libraries to better characterize thyroid autoantigens and demonstrated the feasibility of using recombinant proteins to establish diagnostic assays for autoantibodies.

Antibodies↗
PubMed1989

The Hancock II porcine bioprosthesis. A preliminary report.

From May 1983 to July 1987 a total of 153 Hancock II porcine bioprostheses have been implanted in 130 patients with a mean age of 59 +/- 8 years (range 29 to 76 years). Mitral valve replacement was performed in 72 patients, aortic valve replacement in 35, and mitral-aortic valve replacement in 23. Cumulative follow-up of 121 survivors is 223 patient-years and 100% complete (range 0.4 to 4.5 years). The actuarial survival rate at 4 years is 88% +/- 8% for mitral, 86% +/- 7.8% for aortic, and 84% +/- 8% for mitral-aortic valve replacement. Minor thomboembolism occurred in two patients (0.9% +/- 0.6%/pt-yr) with an actuarial freedom from emboli at 4 years of 100% for mitral, 96% +/- 3.7% for aortic, and 91% +/- 8.6% for mitral-aortic valve replacement. Anticoagulant-related hemorrhage occurred in 10 patients (4.4% +/- 1.4%/pt-yr) with an actuarial freedom at 4 years of 90% +/- 4.8% for mitral, 89% +/- 5.8% for aortic, and 84% +/- 10.6% for mitral-aortic valve replacement. Failure of the porcine bioprosthesis was observed in three patients with an actuarial freedom at 4 years of 96% +/- 3.6% for aortic, 91% +/- 8% for mitral, and 91% +/- 8.6% for mitral-aortic valve replacement. Actuarial freedom from all porcine bioprosthesis-related complications at 4 years is 85.7% +/- 6.6% for aortic, 79% +/- 9% for mitral, and 70% +/- 13% for mitral-aortic valve replacement. No instances of primary tissue failure occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1988

Measurement of TSAb directly in serum using FRTL-5 cells.

FRTL-5 cells were shown to be suitable for the measurement of thyroid stimulating antibody (TSAb) present in sera of patients with Graves' disease. Current methods for the assay of TSAb require the separation of immunoglobulin G (IgG) from patient sera. In this report the possibility to measure TSAb directly on serum was evaluated using FRTL-5 cells. To this purpose cells were seeded in 96-well plates and cultured for 4 days in medium deprived of TSH. Using this system bovine TSH was able to produce a significant stimulation of cAMP production at 1 microU/ml. Whole normal serum completely inhibited the stimulation of TSH as well as that of TSAb, while diluted serum was devoid of any effect. Heat inactivated sera and IgGs, prepared by DEAE Sephadex separation, were diluted in hypotonic medium and incubated with cells for 1 h at 37 C. After incubation cAMP was measured in the assay medium by RIA. In some experiments the effects of graded dilutions of sera and IgGs with known TSAb activity were compared. Sera as well as IgGs increased the cAMP production, but, at the highest concentrations, an inhibitory effect was evident. For this reason sera were tested after appropriate dilution. Thirteen/27 (48%) sera and 22/27 (81%) IgGs from patients with Graves' disease were TSAb positive. The effect of Graves' sera on adenylate cyclase stimulation was completely inhibited by an anti-human IgG. The results of stimulation produced by Graves' sera and IgGs were highly correlated (r = 0.97, p less than 0.001). In conclusion it is possible to measure TSAb directly in serum using FRTL-5 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Autoantibodies to thyroxin and triiodothyronine in the immunoglobulin G fraction of serum.

Thyroid hormone antibodies (THAbs)--i.e., antibodies to thyroxin (T4) and triiodothyronine (T3)--are detected rarely in human serum, where they are searched for, possibly because of a quantitatively minimal interaction between thyroid hormones (the haptens) and serum IgGs (the antibodies). The weak binding could result from these facts: (a) there are already six physiological carrier proteins for thyroid hormones; (b) THAbs usually account for a very small fraction of the total serum IgGs; (c) THAbs may have--as reported in the literature--a relatively low affinity. To ascertain whether THAbs could pass undetected in serum, we measured antibodies to T3 and T4 in both the serum and the corresponding IgG fraction of six normal persons and 45 patients with various thyroid diseases (Graves' disease, idiopathic myxedema, Hashimoto's thyroiditis, subacute thyroiditis, tumors), using radioimmunoprecipitation. The prevalence of antibodies to T4 was 0/51 in both the sera and the IgG fractions; the prevalence of antibodies to T3 was 1/51 in both materials. Because all of the sera that tested THAb negative were confirmed to be so in the THAb assay of the IgG fraction, we conclude that the prevalence of serum THAbs is not underestimated and that autoimmunization against thyroid hormones is really a rare phenomenon.

Autoantibodies↗
PubMed1987

Detection and characterization of autoantibodies blocking the TSH-dependent cAMP production using FRTL-5 cells.

Autoantibodies blocking the TSH-stimulated cAMP production (TBkAb) were measured in immunoglobulin G (IgG) preparations from 38 patients with primary autoimmune hypothyroidism, using FRTL-5 cells. TBkAb were detectable in 15/23 IgG preparations from patients with untreated idiopathic myxedema, and in 2/15 IgGs from patients under L-thyroxine treatment. None of the IgG from 22 normal subjects or from 10 patients with nonautoimmune hypothyroidism following total thyroidectomy caused any significant effect on the TSH-stimulated cAMP production. No correlation was found between TBkAb and the thyroid microsomal antibody. Antibodies inhibiting the 125I-TSH binding to TSH receptor were detectable in only 3/20 patients; IgGs from these 3 patients were also positive in the TBkAb assay. One IgG with potent TBkAb activity inhibited the TSH-stimulated adenylate cyclase in a competitive manner, while it had no effect on the forskolin-stimulated cAMP production. The inhibiting action of this IgG was almost completely lost after preabsorption with human thyroid membranes. In conclusion, we describe a new practical and sensitive method for the measurement of TBkAb; TBkAb are distinct from the microsomal antibody, and are probably directed to the TSH receptor.

Adenylyl Cyclases↗
PubMed1986

Post-coital contraception by estrogen/progestagen combination or IUD insertion.

Five-hundred-thirty-eight patients received a complete follow-up to the first menses after post-coital contraception (PCC). Hormonal contraception (pill) was used in 436 women and mechanical contraception (IUD) was used in 102 women. No pregnancies were observed in the IUD group, while 8 pregnancies were found in the hormonal group. A comparative evaluation of the effectiveness and side effects of the two methods was made. The usefulness of PCC after an unprotected intercourse in order to avoid a pregnancy is confirmed.

Adolescent↗
PubMed1986

[Danazol: a new hormonal post-coital contraceptive method].

During a 9-month period, 84 female patients received post-coital contraception consisting either of an association of ethinyl estradiol/norgestrel or of danazol, in order to compare the safety and any adverse reaction of these 2 treatments. Overall, the patients treated with danazol presented 1/3 as many side effects. Nausea was reduced to 1/3 in frequency and vomiting to 1/9 in this group. 5 pregnancies were confirmed in the ethinyl estradiol/norgesterol group and 2 in the danazol group. Although more cases are needed, it would appear that danazol is characterized by greater efficacy and patient acceptability.

Biology↗
PubMed1984

High-performance liquid chromatographic separation of cadralazine from its potential metabolites and degradation products. Quantitation of the drug in human plasma and urine.

The chromatographic behaviour of cadralazine and its potential metabolites and degradation products with respect to pH, buffer molarity and composition of eluent is described. A selective method with an adequate sensitivity for the determination of the drug in human plasma and urine is also reported. The method includes extraction of biological fluids with chloroform and the analysis of extracts on a reversed-phase column with isocratic elution and detection at 254 nm. The method has been applied to the analysis of plasma and urine of a patient administered a single oral dose of 30 mg of cadralazine.

Antihypertensive Agents↗