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Biomedical subjects

G Medeiros-Neto

Publications and source records attributed to G Medeiros-Neto.

At least 55 records · Page 3Linked to original sources
PubMed1994

Prevalence of anti-thyroid peroxidase antibodies in autoimmune and nonautoimmune thyroid disorders in a relatively low-iodine environment.

We evaluated the prevalence of antithyroid peroxidase antibodies (anti-TP0 Ab) in 402 patients with thyroid disease and 30 healthy controls by a commercial radioimmunoassay (RIA) and compared the results with the passive hemagglutination (HA) method. The patients in the study had autoimmune thyroid disorders (AITD) such as Graves' disease and Hashimoto's disease or had nonautoimmune thyroid diseases (NAITD) such as thyroid cancer, congenital goiter, endemic goiter, and nodular goiter. Subjects were recruited from a population with a mild iodine deficiency (Sao Paulo, Brazil). The effect of specific therapy (for either thyrotoxicosis or chronic thyroiditis) on the circulating anti-TPO levels was also investigated. Positive anti-TPO Ab was detected in 89.9% of the patients with AITD as compared with a prevalence of positive tests of only 4.8% in patients with NAITD. Positive microsomal antibody (M Ab) was found in 68.4% of the patients with AITD and in 6.4% of the patients with NAITD. A positive and significant correlation was obtained between M Ab and anti-TPO Ab. A positive anti-TPO test with negative anti-M was found in 14.1% of the patients with AITD but in only 4.3% of the patients with NAITD and normal controls. These results suggest that anti-TPO Ab by RIA is more sensitive and specific than M Ab by HA. In patients with AITD, anti-TPO Ab levels usually decreased after treatment, suggesting that this parameter could be used in the follow-up of these thyroid disorders.

Antibody Specificity↗
PubMed1994

The effect of hypocaloric diet with and without D-fenfluramine treatment on growth hormone release after growth hormone-releasing factor stimulation in patients with android obesity.

Basal and stimulated growth hormone (GH) secretions are impaired in obesity, and partial restoration of the GH response to various stimuli is observed after weight loss. The aim of the present study was to investigate whether D-fenfluramine, a serotoninergic agent, would increase the GH response to growth hormone-releasing factor (GRF) as compared with placebo in obese android patients. The subjects were 17 patients with android obesity (four men and 13 women) aged 21 to 58 years with a body mass index (BMI) ranging from 32.0 to 52.2 kg/m2 and an abdominal-gluteal ratio greater than 1.0. The following four GRF (1-44) tests were performed: T-30 (control), T0 (after 30 days of a hypocaloric diet), T1 (after 30 days of either placebo or D-fenfluramine 15 mg twice daily), and T2 (after 30 additional days of placebo or D-fenfluramine). The hypocaloric diet was maintained during the T1 and T2 periods. At each test, the serum GH response to GRF was measured at frequent intervals, and the peak GH response and the GH area under the curve were calculated. Serum insulin concentrations were also assayed before GRF stimulation, and the insulin to GH ratio was obtained. The D-fenfluramine-treated group had a mean +/- SEM GH peak level after GRF significantly higher at T1 (43.3 +/- 8.2 micrograms/L) and T2 (50.9 +/- 9.2 micrograms/L) compared with the placebo group. Likewise, the mean integrated areas of GH response were significantly higher for the D-fenfluramine-treated group as compared with the placebo group at both T1 and T2 of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Clinical and molecular genetics studies in Pendred's syndrome.

A large and highly inbred kindred including patients with incomplete and complete forms of Pendred's syndrome was studied. Blood samples were collected from 42 individuals (23 affected and 19 normal), and serum thyroid hormones, TSH, Tg, and anti-TPO autoantibodies were assayed. Thyroid function studies have indicated euthyroidism in all 42 individuals. The affected subjects, however, had significantly elevated serum Tg levels (19.4 +/- 6.8 ng/dL) as compared with normals (9.6 +/- 2.9 ng/dL). Nineteen subjects had clinical and or ultrasonographic evidence of a multinodular goiter. In addition, 13 individuals had impaired hearing with or without goiter. Computer axial tomography scan studies in six patients confirmed the presence of a defective cochlea (Mondini's cochlear defect) in three of these subjects. It has been suggested that thyroperoxidase (TPO) in patients with Pendred's syndrome might be defective for coupling but could be partially effective for iodide organification. We have investigated possible abnormalities in the TPO gene by Southern blot analysis. Genomic DNA was obtained from peripheral blood leukocytes of 40 subjects (22 affected and 18 normal). DNA samples were digested with five restriction enzymes and hybridized with the pM5 probe (831 bp). Polymorphic fragment patterns obtained with three of the five enzymes employed were equally distributed in normal and affected subjects of this kindred. Lod score analysis did not disclose any linkage of TPO gene polymorphisms with the phenotypic characteristics observed in this family. Our findings may be explained in two different ways. First one might have hitherto undetected mutations in the TPO gene, and, second, the pathology may in fact be due to a genetic defect lying elsewhere.

Blotting, Southern↗
PubMed1994

Antithyroid effects in vivo and in vitro of babassu and mandioca: a staple food in goiter areas of Brazil.

Babassu (Orbignya phalerata), a palm-tree coconut fruit, mixed with mandioca (Manihot utilissima) is the staple food of people living in the endemic goiter area of Maranhao in Brazil, where goiter prevalence among schoolchildren was still 38% in 1986 despite an adequate iodine intake in most of the population. Therefore, the question arose as to whether or not the ingestion of babassu alone or mixed with mandioca contributed to the persistence of endemic goiter in this area of Brazil. In this investigation we examined the potential antithyroid effects of babassu and mandioca by means of in vivo studies in Sprague-Dawley rats, in vitro studies in porcine thyroid slices and using a purified porcine thyroid peroxidase (TPO) system. Samples of various edible parts of babassu and mandioca flour were homogenized and extracted in goitrogen-free water (GFW) for in vivo experiments, and in methanol (100 g/l), GFW or 0.06 mol/l phosphate buffer (pH 7.0) for in vitro experiments. The edible parts of babassu produced significant in vivo antithyroid effects (p < 0.05- < 0.001) in rats on a high iodine intake (14 micrograms I- day-1.rat-1), as well as distinct and reproducible antithyroid and anti-TPO activities in both in vitro systems, their action being similar to that of the thionamide-like antithyroid drugs propylthiouracil and methimazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism.

The integrity of the Tg structure as a protein is essential for adequate synthesis of thyroid hormone. Also a large supply of iodine and of thyroid hormone is stored into the Tg molecule and available for secretion on demand. Mutations in Tg gene or hyposialylated Tg due to a defective sialyltransferase activity would cause a structurally defective protein and severely impair the functional ability of Tg. In this review we attempt to cover the abnormalities in the synthesis of Tg described in both animals and man. Hereditary congenital goiter with or without hypothyroidism is the phenotypic major clinical finding in these species. Affected animals include sheep, bovine cattle, bongo antelope, goats, and mice. As in man the inheritance mode is autosomal recessive. In most animal studies structurally abnormal Tg is present. The molecular basis for the defective Tg synthesis was attributable to nonsense mutation in exon 9 (Afrikander cattle) and in exon 8 (Dutch goats). In man the Tg defective synthesis has been reported in 89 subjects and frequently more than one sibling is affected in a given generation. Characteristically these patients exhibit hereditary congenital goiter with relatively low Tg levels that do not increase after stimulation with bovine TSH. High PBI concentrations with low serum T4 values indicate the serum presence of iodinated proteins (mainly iodoalbumin). Also iodinated peptides are frequently excreted into the urine. Tissue studies confirm that there is an absent Tg peak at gel filtration, and virtually no immunoassayable Tg is present in the tissue extracts. The molecular basis of these defects have been recently reported in a patient and includes low tissue Tg mRNA probably due to premature degradation of a defective Tg mRNA. The responsible mutation is a cytosine to thymine transition creating a stop codon at position 1510. The point mutation is removed by the preferential accumulation of a 171 nt deleted Tg mRNA. In another subject molecular studies revealed that exon 4 was missing from the major Tg transcript due to a cytosine to guanine transversion at position minus 3 in the acceptor splice site of intron 3. It is anticipated that other mutations responsible for these defects will be identifiable in the near future.

Amino Acid Sequence↗
PubMed1993

A nonsense mutation causes human hereditary congenital goiter with preferential production of a 171-nucleotide-deleted thyroglobulin ribonucleic acid messenger.

Defective or impaired thyroglobulin (Tg) synthesis usually results in congenital goitrous hypothyroidism, virtual absence of Tg in thyroid tissue, and the presence of an elevated concentration of iodoalbumin. The final result of these abnormalities is a decreased rate of T3 and T4 synthesis. We have previously reported two siblings with this syndrome that was attributable to decreased levels of thyroid tissue Tg mRNA, resulting in decreased translation of a fully mature Tg. Further molecular studies in this family are the subject of this report. The Tg mRNA from normal and goitrous thyroid tissue was first reverse transcribed and divided into five overlapping portions from positions 57-8448, and the resulting cDNAs were amplified by polymerase chain reaction and analyzed by agarose gel electrophoresis. The amplification of nucleotides (nt) 4502-5184 from control thyroid tissue Tg mRNA showed a predominant fragment of 683 basepairs (bp) and a minor fragment of 512 bp. This latter fragment contained a 171-nt deletion that mapped between positions 4567 and 4737 of the Tg mRNA. In contrast, the fragment predominantly present in the congenital goiter was 512 bp. The sequencing of the 683-bp fragment revealed that the responsible mutation is a cytosine to thymine transition, creating a stop codon at position 1510. This results in loss of a TaqI restriction site. The point mutation is, thus, removed from a portion of the transcripts by the preferential accumulation in the goiter of a 171-nt-deleted Tg mRNA. The reading frame is maintained and is potentially fully translatable into a Tg polypeptide chain shorter by 57 residues. The presence of the deleted Tg mRNA in normal thyroid tissue, albeit at a low level, strongly suggests that the deleted mRNA sequence corresponds to a complete exon. Our studies suggest that the shorter, alternatively spliced Tg mRNA predominates in the goitrous tissue and probably has a shorter half-life. This would explain the tissue's low Tg mRNA levels, previously reported. Moreover, translation of the mutated transcript would generate a severely truncated Tg polypeptide with limited ability to generate thyroid hormone, resulting in congenital goitrous hypothyroidism.

Amino Acid Sequence↗
PubMed1993

Treatment of Graves' disease: effects of the administration of L-thyroxine associated with methimazole as a single daily dose.

OBJECTIVES: To reduce the number of tablets to be administered daily during antithyroid drug (ATD) treatment of Graves' disease (GD) and to evaluate the effectiveness of adding thyroxine after the patients had become euthyroid during methimazole therapy. PATIENTS AND METHODS: All patients were given gelatin capsules with 30 mg of methimazole 2 times per day for 4-6 weeks, followed by two capsules with 20 mg of methimazole and 75 micrograms of thyroxine to be taken once a day for 18-24 months. Thirty patients with Graves' disease without previous treatment for hyperthyroidism were included. Two were lost to follow-up and 28 (24 women and 4 men; age range 14-53 years; mean 34.2 years) were followed for 18 to 24 months with methimazole and thyroxine medication plus an additional 2 years after the treatment was suspended. After completion of the study the patients were, retrospectively, divided in two groups: group 1 (G1, n = 20) patients considered to be in remission, and group 2 (G2, n = 8) with persistent active Graves' disease. RESULTS: All patients in group 1 had a significant reduction in the glandular mass, as estimated by ultrasonographic studies (mean +/- SD 67 +/- 13 g to 18 +/- 3 g, p < 0.01) whereas subjects in group 2 had no significant reduction in glandular mass (67 +/- 14 g to 53 +/- 16 g). Thyroglobulin levels (mean +/- SD) in G1 were 54 +/- 55 micrograms/L at baseline and decreased to 15 +/- 9 micrograms/L (p < 0.001), and in G2 thyroglobulin concentrations did not decrease significantly after therapy (58 +/- 20 micrograms/L vs 44 +/- 22 micrograms/L). Also, levels of thyroid-stimulating hormone receptor inhibiting antibody (TRAb) only decreased in G1 (49-21% to 8 +/- 5%; p < 0.001). Nineteen patients (all from G1), were euthyroid 2 years after treatment withdrawal, indicating a remission rate of 67.8%. CONCLUSION: The administration of L-thyroxine during anti-thyroid drug treatment, with subsequent inhibition of thyroid-stimulating hormone secretion, may be an important factor in glandular mass reduction, decreasing both the production of antibodies to thyroid-stimulating hormone receptors and the frequency of recurrence of hyperthyroidism.

Adolescent↗
PubMed1992

Hyposialylated thyroglobulin in a patient with congenital goiter and hypothyroidism.

A large family (14 children) with congenital goiter whose parents are first cousins was studied. Thyroid tissue was obtained, after 125I in vivo labeling, from one of the siblings (JBM). Gel filtration of thyroid proteins indicated that thyroglobulin (Tg) eluted as a single symmetrical peak in the same position as authentic 19S Tg. Gel electrophoresis in a 7.5% sodium dodecyl sulfate-polyacrylamide gel revealed a major band with the same mobility and immunoreactivity as normal 19S Tg. Hydrolysis of the patient's Tg indicated that most of the radioactivity was mono- and diiodotyrosines. The yield of T4 from JBM Tg (26 pmol/mg protein) was 5-fold less than normal thyroid tissue (140 pmol/mg protein) and approximately half of that in thyroid tissue from endemic goiter (51 pmol/mg). Total T3 released from JBM Tg was similar to the other two tissues. When the carbohydrate content of normal and patient Tg was analyzed, there was no differences in glucosamine, galactose or mannose content. However, unlike normal and endemic-goiter Tg, that had a mean sialic acid content of 7.3 and 5.6 micrograms/mg protein, respectively, the sialic acid concentration of the patients Tg was only 0.3 microgram/mg. Sialyltransferase activity was readily demonstrated in homogenate from normal thyroid or endemic goiter, but no sialyltransferase activity was detectable in a homogenate of JBM-thyroid tissue. We conclude that the finding of severely hyposialylated Tg is linked to a defect in iodotyrosine coupling seen in this patient with a possibly abnormal migration of Tg into the follicular lumen.

Carbohydrate Sequence↗
PubMed1991

Normal thyroglobulin and thyroperoxidase gene expression in thyroid congenital defective thyroglobulin synthesis.

We have studied a member (JBM) of a family MO previously described, with congenital goiter, hypothyroidism, and presence of hyposialylated Tg in the follicular lumen. Other congenital goiters (MA and JNA) with virtual absence of Tg were studied similarly. The presence of apparently normal-sized Tg in JBM tissue was confirmed in the present study by radioimmunoassay, Sephacryl S300 column chromatography, immunoelectrophoresis, and SDS agarose gel electrophoresis. Dot blot hybridization analysis with Tg and TPO probes indicated that mRNA hybridization levels of JBM tissue were similar to control thyroid tissues. Congenital goiter tissues showed relatively lower TSH receptor mRNA content in comparison with normal thyroid tissues. DNA was digested with five restriction endonucleases (Taq I, Eco Rv, Pvu II, Pst I, and Eco RI), and the results revealed polymorphisms previously described with the Tg gene. No significant differences in the TPO Pst I pattern were observed in comparison with control samples. We conclude that no major alterations of the Tg and TPO gene expression are detectable and that no significant deletions of these genes are present. The biochemical abnormality in the JBM Tg molecule may be a posttranslational error during the assembly of the protein.

Blotting, Northern↗
PubMed1991

Genetic linkage studies of thyroid peroxidase (TPO) gene in families with TPO deficiency.

We have conducted biochemical and genetic studies in five unrelated families (denoted A, C, R, P, and G), which included nine goitrous subjects (five borderline euthyroid and four hypothyroid) with complete (n = 6) or partial (n = 3) thyroid peroxidase (TPO) deficiency. Thyroid tissue was obtained from four subjects, respectively, in families A, C, and R. No iodide organification or iodide incorporation into protein was present in families A and C. The two affected siblings in family R had a low normal tissue thyroperoxidase activity. Using a 0.8-kilobase (kb) cDNA clone (pM5) encoding 30% of the cDNA of human TPO gene down-stream from basepair 730 and four restriction enzymes (TaqI, PstI, BglI, and BglII), we were unable to find any polymorphisms in family A. In another family (C) blood samples were obtained from only two family members, and consequently, it was not possible to determine linkage. DNA from families G, P, and C showed biallelic polymorphisms when digested with BglII, at 8.7 and 8.5 kb. In family R we detected two biallelic polymorphisms at 9.0 and 8.5 kb, and the 9.0-kb bands were clearly larger than 8.7-kb bands found in the other subjects. Also, there was an absence of a 4.0- to 3.9-kb band that may represent a partial gene deletion. With PstI-restricted DNA a possible deletion of 5.5-kb band was also present in affected siblings of family R. The logarithm of odds (Lod) score analyzed from the family with inbreeding (R) was compatible with linkage of disease and the TPO gene (Lod = 2.08). When this method was used with families G and P, the Lod score was inconsistent with linkage between disease and the TPO gene. These data suggest that the cause of TPO deficiency in these families is heterogeneous. However, the restriction fragment length polymorphism pattern of BglII-restricted DNA in the R family strongly suggests that a partial TPO gene deletion has occurred in this family.

Bacterial Proteins↗
PubMed1991

Immunologically mediated cytotoxicity against human eye muscle and thyroid cells in euthyroid and thyrotoxic Graves' ophthalmopathy.

We have studied the role of eye muscle and thyroid autoimmunity in patients with Graves' hyperthyroidism with or without ophthalmopathy in an area of relatively low iodine intake. Antibody dependent cell mediated cytotoxicity (ADCC) and complement mediated antibody dependent cytotoxicity (CMAC) against thyroid and eye muscle cells, and levels of antibodies against TSH receptor antigen and the thyroid microsomal antigen (thyroid peroxidase) were determined in three groups of patients: (1) thyrotoxic with exophthalmos (TX, n = 28), (2) thyrotoxic without ophthalmopathy (GR, n = 10), and (3) euthyroid ophthalmopathy (EU, n = 12). The thyroid glandular mass of the EU group was significantly less (P less than 0.01) compared with TX or GR. Mean (+/- SD) TSH receptor antibody (TRAb) level was 27 +/- 14% in EU which was significantly lower compared with TX (52.4 +/- 20%) and GR (59 +/- 18%). The prevalence of microsomal antibodies were similar and not significantly different in the three groups. On the other hand the prevalence of positive ADCC and CMAC tests was significantly greater, and at higher levels, in EU (ADCC THY CELLS 10.9 +/- 8.9% SL, ADCC Eye muscle = 25.9 +/- 20% SL, CMAC = 70.2 +/- 43% SL) and TX (ADCC THY CELLS = 9.3 +/- 9.2% SL, ADCC Eye muscle = 20.1 +/- 19% SL, CMAC = 62.4 +/- 30% SL) compared to GR (ADCC THY CELLS = 4.4 +/- 9.5% SL, ADCC Eye muscle = 7.7 +/- 6.7% SL, CMAC = 24.7 +/- 23% SL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Thyroid atrophy in myxedematous endemic cretinism: possible role for growth-blocking immunoglobulins.

We have examined the ability of IgGs obtained from 8 endemic cretins to inhibit TSH-stimulated thyroid cell growth in culture. Clinical and laboratory evidence for hypothyroidism was present in six subjects; the two remaining patients had borderline low serum T4, normal T3 and exaggerated TSH response to TRH. In six patients 2 mg IgG exhibited an inhibitory effect in the cellular growth expressed by a diminished incorporation of 3H-thymidine into the DNA of TSH-stimulated FRTL-5 cells (range: 26-87% inhibition). Seven patients presented clinically with thyroid atrophy of relatively small thyroid enlargements for the degree of chronic iodine deficiency that was present in the area. The remaining subject had a large multinodular goiter and IgG purified from this patient had no inhibitory effect in the FRTL-5 cellular growth. A direct relationship was noted between the degree of thyroid growth inhibition (%) and the basal serum TSH concentration. We conclude that the presence of thyroid growth inhibiting immunoglobulin may be related to the absence of thyroid growth or even thyroid atrophy in endemic cretins.

Adolescent↗
PubMed1989

Natural course of iodine-induced thyrotoxicosis (Jodbasedow) in endemic goiter area: a 5 year follow-up.

In the Balsas region of North Brazil (85% prevalence of goiter), 1876 goitrous subjects (1663 with goiter grade I and II and 103 with grade III multinodular goiter) were treated with 1 ml of iodized oil im (l-oil). From the population with grade III goiter we were able to follow-up for 5 yr 13 euthyroid goitrous patients (group 1) and 8 goitrous individuals (group 2) who developed iodine-induced thyrotoxicosis (IIT, 0.42% of the total population or 7.76% of the multinodular goiter subjects). The two groups were matched for age and goiter size, and had no significant differences in the baseline levels of thyroid hormone concentration, T3/T4 ratio or mean serum TSH. However, group 2 had a higher concentration of serum Tg, and 48 h after challenge with 10 U of bovine TSH (bTSH) had a significantly higher absolute release of T3 and Tg than group 1. In 4 patients IIT was transitory and resolved by 12 months. Four other subjects, however, maintained a mild clinical form of IIT that only normalized at 50 months. Only one patient needed treatment with methylmercaptoimidazol. There was no evidence of autoantibodies (TSH-receptor inhibiting antibody, anti-Tg or anti-microsomal antibodies) against thyroid antigens in group 2 patients. All subjects, including those with thyrotoxicosis, showed a remarkable shrinkage of the goiter by 60 months which was reflected by a significantly lower absolute response of T3 and Tg after bTSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Brazil↗