Analysis of inherited genetic variants in ret proto-oncogene of Brazilian patients with apparently sporadic medullary thyroid carcinoma.

Mutations in different exons of ret proto-oncogene are responsible for the development of medullary thyroid carcinoma (MTC). The mutations can occur as sporadic or as part of multiple endocrine neoplasia (MEN) type 2 hereditary syndromes. Here we report the first focused study of sporadic MTC in Brazilian patients regarding clinical and molecular analysis of ret proto-oncogene. Our study seeks to estimate the risk of hereditary MTC cases among apparently sporadic cases in a Brazilian population and describe ret genetic variants in their germinative lineage. Germinative sequence variants were screened by DNA sequencing and denaturing gradient gel electrophoresis (DGGE) analysis of exons 10, 11, 13, 14, 15, and 16 of 24 Brazilian patients with apparently sporadic MTC. We identified 1 inherited case of 24 (4%) patients with apparently sporadic MTC. Polymorphisms for the ret proto-oncogene coding region were identified in codon 769 of exon 13 (LeuCTT--> LeuCTG) at a frequency of 13% (3/24) and in codon 904 of exon 15 (SerTCC--> SerTCG) at a frequency of 16.6% (4/24). The observed frequency (4%) of inherited disease among apparent sporadic MTC strengthens routine application of ret proto-oncogene germinative DNA screening in all cases of apparently sporadic MTC ascertained at Brazilian cancer hospitals.

Occupational allergy caused by carnation (Dianthus caryophyllus).

BACKGROUND: Occupational respiratory symptoms caused by decorative flowers are seldom reported in the literature. In our area a large portion of the population works in carnation (Dianthus caryophyllus) winter quarters, and many workers have symptoms of rhinitis and asthma related to exposition. OBJECTIVE: The purposes of this study were to investigate whether the symptoms induced by carnation were IgE-mediated and to study the possible allergens involved. METHODS: A total of 16 subjects employed in indoor carnation cultivation with symptoms during exposition time were studied along with 15 patients with allergic asthma who were not exposed to carnations and 15 healthy carnation workers used as control subjects. Skin prick tests with carnation extract and RASTs were performed. Protein bands were isolated by SDS-PAGE, and afterwards immunoblotting was performed to characterize the extract. Specific nasal provocation and nonspecific bronchial provocation tests were performed for all the asthmatic patients. Diurnal variation in peak expiratory flow was also measured. RESULTS: Skin prick test responses with carnation extract were positive in 15 of the 16 patients and negative in all control subjects. Nasal provocation test responses with carnation extract were positive in 13 of 16 patients. A significant correlation was seen between RAST and nasal provocation results (P <.01). Immunoblotting of sera from 13 patients showed 2 major IgE-binding fractions of 34 and 35 kd in most of the patients, which could constitute the major allergen. Methacholine PD20 showed a variable degree of nonspecific bronchial hyperresponsiveness in all asthmatic subjects. CONCLUSION: Data demonstrate the involvement of carnation in occupational allergy, mediated by an IgE-dependent mechanism.

Co-stimulation of cultured peripheral blood mononuclear cells from intrinsic asthmatics with exogenous recombinant IL-6 produce high levels of IL-4-dependent IgE.

Asthma is an inflammatory airway disorder, traditionally subdivided into extrinsic, immunoglobulin E (IgE)-mediated, and intrinsic asthma of unknown aetiology. IgE synthesis requires contact between T- and B-cells and a signal provided by interleukin (IL)-4, which can be modulated by IL-6. The objective of this study was to evaluate the effects of IL-4 and IL-6 on total IgE synthesis by peripheral blood mononuclear cells from intrinsic and extrinsic asthmatics. Peripheral blood mononuclear cells from intrinsic and extrinsic asthmatic patients and from healthy subjects were cultured and stimulated with pokeweed mitogen, recombinant IL-4 and IL-6. The IgE level in serum and supernatants was measured by an enzyme-linked immunoassay. Serum IgE was significantly lower in intrinsic asthma than in extrinsic asthma, but significantly higher than in control subjects. IgE production by cultured mononuclear cells from extrinsic asthmatics was not modified after exogenous IL-4 and IL-6 addition. However, intrinsic asthmatics showed enhancement of IgE synthesis in response to IL-4 stimulation, reaching a threefold increase of the spontaneous IgE values, when simultaneous recombinant IL-4 plus IL-6 stimulus was used. Our results indicate that exogenous recombinant interleukin-6 can significantly upregulate the interleukin-4-dependent immunoglobulin E synthesis in intrinsic asthma. This suggests that immunoglobulin E could also play a role in the pathogenesis of intrinsic asthma, in which an interleukin-6 threshold would be critical.

Cost-effectiveness of various methods of diagnosing hypersensitivity to Alternaria.

This study was undertaken for two reasons: 1) It is more difficult to diagnose hypersensitivity to molds than to other allergens, so an evaluation of diagnostic tests was needed. 2) Alternaria is the principal cause of mold sensitization in our area. Sixty-six patients (20 +/- 4 years) were selected and divided into two groups. Group A was made up of patients with rhinitis and/or asthma due to Alternaria sensitization. Group B consisted of patients sensitized to other allergens and patients with nonrespiratory allergic disorders. Skin tests (prick and intradermal), challenge tests (conjunctival, nasal, and bronchial), and specific IgE determination were performed for all patients. A biologically standardized extract of Alternaria tenuis (Alergia e Inmunología Abelló, S. A., Madrid, Spain) obtained from a single batch was used for all tests. Our diagnostic criterion was a clinical history of rhinitis or asthma that coincided with the results of nasal/bronchial challenge. The diagnostic value of the other tests was compared to this criterion. In the group of rhinitic patients, skin tests and conjunctival challenge were more sensitive than specific IgE determination. In asthmatic patients, the most sensitive techniques were nasal and conjunctival challenges, followed by prick and intradermal skin tests, and, lastly, serum specific IgE determination. When rhinitis and asthma were considered jointly, the most sensitive test was conjunctival challenge, followed by skin-prick and intradermal tests. All tests had the same specificity, regardless of disorder. Nasal challenge was positive in all patients. Skin tests are easy to perform, cheap, non-traumatic for the patient, and sufficiently specific and sensitive for the diagnosis of Alternaria hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)