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C Giuliani

Publications and source records attributed to C Giuliani.

30 records · Page 2Linked to original sources
PubMed1992

Molecular basis for the autoreactivity against thyroid stimulating hormone receptor.

The present report identifies an important immunogenic region of the TSH receptor and determinants on the TSH receptor for the two types of autoantibodies seen in hyperthyroid Graves' disease and hypothyroid idiopathic myxedema, TSAbs and TSBAbs, respectively. The immunogenic domain with no important functional determinants, is contained within residues 303-382 and involves residues 352-366 in particular. There are determinants flanking the immunogenic domain on the C-terminal portion of the receptor which are the TSBAb and high affinity TSH binding sites: residues 295-306, 387-395, and tyrosine 385. Determinants on the N-terminal portion of the external domain, centered on residues 38-45, are TSAb interactions linked to low affinity TSH binding important for signal generation: threonine 40 and residues 30-33, 34-37, 42-45, 52-56, and 58-61. These determinants are conserved in human and rat receptors, are not present in gonadotropin receptors, and are each related to separate actions of TSH: binding vs. signal generation. They can, therefore, account for organ specific autoimmunity and the different disease expression effected by TSBAbs vs TSAbs, i.e. hypo- vs. hyperthyroidism, respectively. It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase. Inappropriately high class I expression in the thyroid, i.e. if induced by interferon, viruses, or some as yet unknown agent, would contribute to the generation of autoimmune disease. Thus, it would result in increased antigen presentation to the immune system, particularly those autoantigens increased by TSH and its cAMP signal such as thyroglobulin or thyroid peroxidase, or whose turnover is increased by TSH and its cAMP signal, such as the TSH receptor. In the case of the latter, peptide 352-366, known to be near a protease sensitive site on the receptor [41,49], would now act as a potent self-antigen and induce the formation of receptor autoantibodies. It is further proposed that methimazole and high doses of iodide are therapeutically effective agents in thyroid autoimmune disease because they, in part, decrease MHC class I gene expression. Speculation is presented which suggests that elimination of negative regulation of MHC class I and the TSH receptor is an important factor in the development of autoimmune thyroid disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

Growth delay in Down syndrome and zinc sulphate supplementation.

Children affected with Down syndrome (DS) show deficient growth, immunodeficiency--especially concerning the T-cell population--and low plasma zinc levels. New growth charts have been recently proposed, and zinc supplementation to the diet has been reported to improve transiently the efficiency of the immune system. The aim of this study was to evaluate if in DS children zinc sulphate therapy could improve the growth rate and affect some endocrine parameters. We studied 22 patients (16 males and 6 females) who received zinc sulphate for 6 to 9 months. Fifteen of 22 patients studied reached a higher centile in their growth rate, whereas the remaining seven showed no change, at least to date. The average height velocity changed from 23.84 +/- 7.98 mm/6 months to 40.80 +/- 7.68 mm/6 months. Growth hormone serum level was 5.94 +/- 4.89 ng/ml compared with 7.49 +/- 6.75 ng/ml before and after therapy, respectively. Somatomedin serum level was 160.27 +/- 68.88 mU/ml and 205 +/- 124.07 mU/ml before and after therapy, respectively. In conclusion, zinc sulphate therapy of patients with DS affects not only the immune system, as previously reported, but can also accelerate growth.

Adolescent↗
PubMed1986

The genome of bovine herpesvirus 1 (BHV-1) strains exhibiting a neuropathogenic potential compared to known BHV-1 strains by restriction site mapping and cross-hybridization.

Bovine herpesvirus 1 (BHV-1) strains can be differentiated by their DNA and polypeptide patterns, and by antigenic properties as demonstrated by monoclonal antibodies. We classified the BHV-1 strains according to these data as BHV-1.1, BHV-1.2 (a/b) and BHV-1.3 (a/b). BHV-1.1 and BHV-1.2 correspond to the well known 'common' BHV-1 strains, whereas BHV-1.3 has only recently been recognized and exhibits a neuropathogenic potential. In the present paper we describe the structural genome characteristics of BHV-1.3 compared to those of the other BHV-1 strains, examined by means of restriction site mapping, electron microscopy and cross-hybridization. Our results also confirm and complete data concerning BHV-1.1 and BHV-1.2 published by other authors. The following main conclusions can be drawn from our investigations: BHV-1.1 and BHV-1.2 differences are restricted to distinct genomic regions, characterized by loss or gain of restriction sites. BHV-1.3, however, differs from the other BHV-1 strains in restriction site alterations throughout the whole genome. Electron microscopy showed the typical BHV-1 DNA structure for BHV-1.3. Genetic homology between BHV-1.1 and BHV-1.2, reported to be about 95%, was confirmed by cross-hybridization, and a similar high base sequence homology for BHV-1.3 could be shown.

Animals↗
PubMed1980

Purification of sea-urchin RNA polymerase II. Characterization by template requirements and sensitivity to inhibitors.

The purification of RNA polymerase II from gastrulae of Paracentrotus lividus is described. The enzyme obtained is homogeneous as judged by electrophoresis under non-denaturing conditions. It is able to transcribe both native high-Mr P. lividus DNA and Psammechinus miliaris h22 histone DNA, although single-stranded and nicked DNAs are better templates. P. lividus RNA polymerase II forms with homologous native DNA stable binary complexes that are able to initiate RNA chains after exposure to heparin. Heparin-resistant complexes do not form on nicks of DNA molecules. Sensitivity of sea-urchin RNA polymerase II to rifamycin derivatives and alpha-amanitin has been determined.

Amanitins↗
PubMedDate not supplied

[The clinical use of human recombinant TSH].

The recent cloning of human TSH-beta gene has allowed the production of recombinant human TSH (rhTSH) by recombinant DNA technology in mammalian cells (Chinese hamster ovary cells). Studies aimed at biochemical and biological characterization have shown that rhTSH, unlike pituitary TSH, is highly sialylated and is biological active in stimulating c-AMP accumulation in FRTL-5 cells. Phase I/II and phase III clinical studies have been performed to evaluate the safety and efficacy of rhTSH in stimulating radioactive iodine uptake in patients after total thyroidectomy for differentiated thyroid cancer. In these patients therapy with thyroid hormones is performed to replace hormone production and to suppress TSH-stimulated tumor growth. To detect residual or recurrent cancer, the therapy has to be withdrawn in order to obtain rise in endogenous TSH to perform a total body scan. rhTSH, as a source of exogenous human TSH, has been shown as an additional diagnostic tool in the follow-up of patients with thyroid cancer. Used in patients maintained on thyroid hormone suppressive therapy, rhTSH enhances the sensitivity of serum Tg testing. Although the sensitivity of scans obtained after rhTSH administration is slightly lower than that after thyroid hormone withdrawal, the use of rhTSH avoids the clinical signs and symptom of hypothyroidism and can be used in selected patients.

Carcinoma↗
PubMedDate not supplied

[Nf-kB transcription factor: role in the pathogenesis of inflammatory, autoimmune, and neoplastic diseases and therapy implications].

PURPOSE: Description of the involvement of the transcription factor NF-kB in inflammatory, autoimmune and neoplastic processes. Clinical implications from basic research. DESIGN: Review of the most significant data reported in the literature and personal publications. RESULTS: NF-kB is an ubiquitous transcription factor member of the proto-oncogene family rel. NF-kB regulates the expression of several genes involved in inflammatory and immune responses. The classical activated form of NF-kB consists of the p50/p65 heterodimer, different dimers may be formed with members of rel, AP1, steroid hormones receptors family. Many studies suggest that NF-kB should be considered as an important mechanisms of inflammatory processes and autoimmune diseases. Many important anti-inflammatory drugs and immunosuppressants inhibit NF-kB. Several observations have suggested a role of the inappropriate activation of NF-kB in cell proliferation, transformation, and tumor development, mainly lymphomas. Conversely, it has been proposed that the activation of NF-kB in immune cells may contribute to anti-tumor immunity. CONCLUSIONS: NF-kB is an optimal target of anti-inflammatory and immunosuppresant therapies. Molecular studies on NF-kB are very important to understand the pathogenesis of inflammatory, autoimmune and neoplastic diseases, and to identify new drugs that inhibit NF-kB activation.

Autoimmune Diseases↗
PubMedDate not supplied

[Autonomous thyroid nodule: relations between clinical symptomatology and goiter endemia].

Sixty-three patients with autonomous thyroid nodule were studied, thirty-five from an endemic goiter area (EA) and twenty-eight from a non-endemic goiter area (NEA). Clinical history, physical examination, ultrasonography, thyroid hormone levels, and fine needle aspiration (FNA), were utilized to investigate whether or not iodine deficiency determined differences in the latency of progression to toxicity, the seriousness of illness and thyroid hormone levels. No significant difference was observed in the age of onset of nodularity, while the latency of progression to toxicity was significantly decreased in the EA (p less than 0.001). The ultrasonographic pattern did not show significant volume variations between the EA and NEA, but there was a slight prevalence of multinodular lesions in EA. No significant difference in serum thyroid hormone levels was found between the two areas in non toxic patients, while at the onset of hyperthyroidism higher levels of FT were observed in the EA than in the NEA. FNA showed a prevalence of colloid lesions in EA, while hyperplastic lesions prevail in the NEA. Forty-two patients underwent surgery: the extent of surgery was greater in patients from the EA. In conclusion, in iodine deficient areas earlier clinical thyrotoxicosis and a higher prevalence of hypoactive thyroid nodules were observed. Furthermore, in EA, the autonomous nodule in non toxic phase is more frequently associated with colloid lesions than hyperplastic lesions.

Adult↗
PubMedDate not supplied

Centralized cytogenetic analysis of pediatric acute leukemia: results of an Italian collaborative experience.

BACKGROUND AND OBJECTIVE: Cytogenetic analysis of acute leukemia yields important information which has been demonstrated to be correlated to patient survival. A reference laboratory was created in order to perform karyotype analysis on all cases of acute leukemia enrolled in the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica) protocols. METHODS: From January 1990 to December 1995, 1115 samples of children with ALL or AML were sent in for cytogenetic analysis. The results of cell cultures were screened in the Reference Laboratory and then the fixed metaphases were sent to one of the six cytogenetic laboratories for analysis. RESULTS: The leukemic karyotypes of 556 patients were successfully analyzed. An abnormal clone was detected in 49% of cases of ALL and in 66% of AML. In ALL the most frequent abnormality was 9p rearrangement. Other recurrent abnormalities were t(9;22), t(4;11) and t(1;19). In AML t(8;21), t(15;17) and 11q23 rearrangement were the most frequent structural abnormalities. These findings are similar to the results obtained in other multicenter studies using a similar approach. INTERPRETATION AND CONCLUSIONS: Our data confirm the feasibility of performing cytogenetic analysis in a centralized laboratory on mailed samples of bone marrow and/or peripheral blood; this is very important considering that cytogenetic analysis of neoplastic tissue requires a special laboratory and expert staff.

Acute Disease↗