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Biomedical subjects

C R Nogueira

Publications and source records attributed to C R Nogueira.

18 recordsLinked to original sources
PubMed2007

Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in severely food-restricted rats.

We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2), phospholamban (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 +/- 0.48 vs food-restricted group = 4.84 +/- 0.33, P < 0.01). The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 +/- 0.44 vs food-restricted group = 7.96 +/- 0.45, and control = 1.52 +/- 0.06 vs food-restricted group = 1.53 +/- 0.10, respectively). Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release.

Animals↗
PubMed2005

Profile of thyroid hormones in breast cancer patients.

Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22) were analyzed for free triiodothyronine (T3F), free thyroxine (T4F), thyroid-stimulating hormone (TSH), antiperoxidase antibody (TPO), and estradiol (E2). Estrogen receptor ss (ERss) was determined in tumor tissues by immunohistochemistry. Thyroid disease incidence was higher in patients than in controls (58 vs 18%, P < 0.05). Subclinical hyperthyroidism was the most frequent disorder in patients (31%); hypothyroidism (8%) and positive anti-TPO antibodies (19%) were also found. Subclinical hypothyroidism was the only dysfunction (18%) found in controls. Hyperthyroidism was associated with postmenopausal patients, as shown by significantly higher mean T3 and T4 values and lower TSH levels in this group of breast cancer patients than in controls. The majority of positive ERss tumors were clustered in the postmenopausal patients and all cases presenting subclinical hyperthyroidism in this subgroup concomitantly exhibited Erss-positive tumors. Subclinical hyperthyroidism was present in only one of 6 premenopausal patients. We show here that postmenopausal breast cancer patients have a significantly increased thyroid hormone/E2 ratio (P < 0.05), suggesting a possible tumor growth-promoting effect caused by this misbalance.

Adult↗
PubMed2005

Low triiodothyronine (T3) or reverse triiodothyronine (rT3) syndrome modifies gene expression in rats with congestive heart failure.

Heart failure (HF) is frequently associated with euthyroid "sick" syndrome (low T3 and elevated rT3). We investigated if altered thyroid hormone in HF could affect expression of the TH receptor (TRalpha1), and alpha and beta myosin heavy chains (alpha-MHC, beta-MHC). HF was provoked in rats by aortic stenosis. We showed that rT3 generated from liver and kidney deiodination significantly increased and T3 decreased in HF; there was significantly higher TRalpha1 expression, no alpha-MHC expression, but beta-MHC expression. Changes in TRalpha could be compensating for low T3 from HF.

Animals↗
PubMed2001

Tumor grade heterogeneity in urothelial bladder carcinoma--proposal of a system using combined numbers.

OBJECTIVE: There is no consensus for grading when more than one grade is present in bladder carcinoma. We propose a grading system that considers the primary (most common) and secondary (second most common) grade of bladder cancer. Grade was correlated with stage of the tumors. MATERIAL AND METHODS: We studied 293 bladder transurethral resections or radical cystectomies. Grade was considered as 1, 2 or 3 according to the 1999 World Health Organization system. The number was repeated when only one grade was seen. A final score was obtained which ranged from 2 to 6. All cases were also graded according to the highest grade area even if it was focal. RESULTS: According to the highest grade area, the distribution was 80 (74.07%), 27 (25.00%) and 1 (0.92%) for grade 1; 31 (24.03%), 69 (53.48%) and 29 (22.48%) for grade 2; and 0 (0%), 17 (30.35%) and 39 (69.64%) for grade 3, corresponding to the stages Ta, T1 and T2-T3, respectively. Using the system of combined numbers, grade 2 was stratified into subgroups 1 + 2 and 2 + 2 which are statistically different (p < 0.05) when considering stage. In grade 3, there was also a trend for statistical difference (p = 0.066) between grades 2 + 3 and 3 + 3. CONCLUSIONS: The grading system of combined numbers, stratifies grade 2 into subgroups 1 + 2 and 2 + 2, and grade 3 into subgroups 2 + 3 and 3 + 3 which are statistically different when considering stage. This grading system of combined numbers takes into consideration tumor heterogeneity and may be of value in prospective studies for analysis of prognosis and therapeutic response.

Carcinoma, Transitional Cell↗
PubMed2001

A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child.

Congenital hypothyroidism associated with thyroid hypoplasia can be caused by several genetic defects, including mutations in the TSHbeta-subunit, the TSH receptor, the G(s)alpha-subunit, and the transcription factor PAX8. Four girls with sporadic congenital hypothyroidism and hypoplastic thyroid glands were analyzed for mutations in PAX8 and TTF2 (FKHL15). Mutations in the coding region of the TSHbeta-subunit gene, the TSH receptor gene, and exons 8 and 9 of G(s)alpha had been excluded previously. Serum TSH concentrations were 150 mU/liter or more, TG levels were within normal limits, and thyroid autoantibodies were absent. Technetium scintigraphies did not reveal the presence of thyroid tissue, but ultrasonography documented hypoplastic, normally located glands. One patient was found to harbor a heterozygous transversion 119A-->C in exon 3 of PAX8 replacing a conserved glutamine by proline in the paired box domain (Q40P). Analysis of her family members revealed that her mother, who has a thyroid gland of normal size and mild, adult-onset autoimmune hypothyroidism, is also heterozygous for this mutation. Functional analyses of the PAX8 Q40P mutation showed impaired binding to a PAX8 response element and absent trans-activation of a thyroid peroxidase promoter luciferase reporter gene. These findings confirm the important role of PAX8 in the development of the thyroid, but they indicate that PAX8 gene mutations may have a variable penetrance or expressivity. The absence of mutations in the coding sequences of the analyzed genes in the three other patients supports the concept that the pathogenesis of congenital hypothyroidism associated with thyroid hypoplasia is diverse.

Amino Acid Sequence↗
PubMed2001

Clinical and laboratory evaluation of hyperlipemic and hypothyroid patients.

OBJECTIVE: To determine the frequency of hypothyroidism in a sample of hyperlipemic patients and evaluate clinical and laboratory factors indicative of thyropathy among them. METHODS: Fifty-one hyperlipemic patients, grouped according to an earlier or recent diagnosis of their thyroid function into euthyroid and hypothyroid, were evaluated with clinical and laboratory examinations of blood levels of free T4 and TSH (by radioimmunoassay). Patients were on average 46.8 +/- 11.7 years old, predominantly of the female sex (62.5 %); 31 % had a previous diagnosis of hypothyroidism and were under treatment with thyroxin. RESULTS: Fourteen three percent of patients analyzed had hypothyroidism, which had not been detected before. Differentiating attributes of the groups analyzed were: a predominance of females among the hypothyroid patients and a higher HDL serum concentration among those recently diagnosed. CONCLUSION: In the present study, new cases of hypothyroidism in hyperlipemic patients were a frequent occurrence, yet few clinical and laboratory data except tests evaluating free T4 and TSH in the blood indicated which patients had thyroid dysfunction.

Analysis of Variance↗
PubMed1999

Combined pituitary hormone deficiency in an inbred Brazilian kindred associated with a mutation in the PROP-1 gene.

Mutations in the pituitary-specific paired-like homeodomain transcription factor PROP-1 result in combined pituitary hormone deficiency (CPHD) which includes all anterior pituitary hormones with the exception of ACTH. In an inbred pedigree with CPHD, direct sequencing of the PROP-1 gene revealed a deletion of two base pairs (301-302delAG) in exon 2, resulting in a frameshift and a premature stop in codon 109 in the homeodomain. The clinical characteristics of this family support the notion that this truncation results in a more severe phenotype than missense mutations in the aminoterminal part of the homeodomain.

Adult↗
PubMed1999

Thyrotropin receptor mutations in hyperfunctioning thyroid adenomas from Brazil.

Constitutively activating mutations in the thyrotropin (TSH) receptor have been identified as a major molecular cause of hyperfunctioning thyroid adenomas. A smaller subset of these benign tumors is caused by constitutive activation of the adenylyl cyclase cascade by somatic mutations in the Gsalpha gene. In this study, we analyzed hyperfunctioning thyroid adenomas from seven Brazilian patients for TSH receptor and G(s)alpha gene mutations. Solitary autonomous thyroid adenomas were identified by ultrasound and scintigraphy, and DNA was extracted from adenomatous and periadenomatous tissue. Exons 9 and 10 of the TSH receptor gene, and exons 8 and 9 of the G(s)alpha gene, were amplified by polymerase chain reaction (PCR) and subjected to direct sequence analysis. Six of seven adenomas harbored heterozygous mutations known to confer constitutive activity to the TSH receptor. In one case, aspartate 619 was substituted by glycine (D619G). In four adenomas, alanine 623 was replaced by valine (A623V). Both residues are located in the third intracellular loop. In one instance, aspartate 633 located in the sixth transmembrane domain was replaced by tyrosine (D633Y). In this patient, one allele also contained a change of aspartate 727 to glutamate (D727E). This substitution is thought to be a polymorphic variant of the wild-type but it has also been associated with toxic multinodular goiters. Functional comparison of D727 with E727 did not reveal differences in basal or TSH-stimulated cyclic adenosine monophosphate (cAMP)-dependent luciferase activity in transiently transfected cells. These results demonstrate a high prevalence of activating TSH receptor mutations in toxic adenomas in this small series from Brazil (approximately 86%). These findings are in agreement with reports from other countries with a marginal iodine intake but contrast with studies from regions with a high iodine intake where these mutations appear to be less prevalent.

Adenoma↗
PubMed1999

Structural analysis of the thyrotropin receptor in four patients with congenital hypothyroidism due to thyroid hypoplasia.

Sporadic congenital hypothyroidism is most commonly caused by developmental abnormalities of the thyroid gland. More rarely, it is due to defects in gene products involved in the regulation of the hypothalamic-pituitary-thyroid axis or thyroid hormone synthesis. Loss of function mutations in the thyrotropin (TSH) receptor have been shown to result in resistance to biologically active TSH. In complete resistance to TSH, the thyroid gland is hypoplastic and unable to synthesize and secrete sufficient amounts of thyroid hormones. In partial resistance, referred to as euthyroid hyperthyrotropinemia, the size of the gland and the thyroid hormone levels are normal at the expense of an elevated TSH. Four patients with sporadic congenital hypothyroidism and properly located hypoplastic thyroid glands were included in this study. Serum TSH concentrations were 150 mU/L or higher, serum thyroglobulin levels were within normal limits (6.1 to 8.2 ng/mL; normal range: 2.1 to 32 ng/mL), and thyroid autoantibodies were absent. The coding region of the TSHbeta subunit gene, the TSH receptor gene, and exons 8 and 9 of Gsalpha were analyzed by direct sequencing and found to be normal in all patients. One patient was heterozygous for a G to A transition in the TSHbeta gene resulting in a substitution of alanine by threonine at position -7 of the signal peptide. This substitution was also found in her euthyroid father. In addition, Southern analysis of the TSH receptor gene excluded major structural alterations. These findings support previous reports that indicate that TSH resistance is genetically heterogeneous. In addition to mutations in the TSH receptor or the Gsalpha genes, other genetic defects can lead to an identical phenotype. These observations also suggest that TSH receptor mutations might be a relatively rare cause of congenital thyroid hypoplasia.

Blotting, Southern↗
PubMed1998

Autosomal recessive deficiency of combined pituitary hormones (except ACTH) in a consanguineous Brazilian kindred.

Familial hypopituitarism represents a clinically and genetically heterogeneous disorder. In a subset of these families, defects in Pit-I, a transcription factor essential for proper pituitary development have been identified as underlying molecular cause. These patients present extreme short stature, GH, PRL and TSH deficiency but intact ACTH, LH and FSH secretion. The pituitary is usually hypoplastic. In this report we describe a consanguineous family (the parents are first cousins) with thirteen siblings. Of the ten living siblings, four (two males and two females) have panhypopituitarism with severe growth failure. They had evidence of growth hormone, prolactin and gonadotropin deficiencies and developed central hypothyroidism late in life. ACTH secretion was normal. Bone age was retarded and dual-photon bone densitometry indicated severe osteoporosis. Combined provocative tests for pituitary hormones indicated blunted responses for GH, LH, FSH and a modest rise in serum PRL and TSH. A clonidine-test failed to induce pituitary GH response. A corticotropin-releasing factor (CRF) provocative test was conducted after 6 months without the use of prednisone with a normal ACTH response after CRF in the affected sibling. Plasma IGF-I and IGF-BP3 were below normal levels. Serum E2 (females) and serum testosterone (males) levels were very low. MRI evaluation of the pituitary indicated pituitary aplasia in all subjects. The phenotype described in this kindred is different from families reported with Pit-1 mutations. However, it resembles previously published kindreds with similar clinical and biochemical findings. The relative preservation of ACTH suggests a genetic defect early in pituitary gland development.

Adolescent↗
PubMed1997

Autosomal recessive deficiency of combined pituitary hormones (except ACTH) in a consanguineous Brazilian kindred.

Familial hypopituitarism represents a clinically and genetically heterogeneous disorder. In a subset of these families, defects in Pit-I, a transcription factor essential for proper pituitary development have been identified as underlying molecular cause. These patients present extreme short stature, GH, PRL and TSH deficiency but intact ACTH, LH and FSH secretion. The pituitary is usually hypoplastic. In this report we describe a consanguineous family (the parents are first cousins) with thirteen siblings. Of the ten living siblings, four (two males and two females) have panhypopituitarism with severe growth failure. They had evidence of growth hormone, prolactin and gonadotropin deficiencies and developed central hypothyroidism late in life. ACTH secretion was normal. Bone age was retarded and dual-photon bone densitometry indicated severe osteoporosis. Combined provocative tests for pituitary hormones indicated blunted responses for GH, LH, FSH and a modest rise in serum PRL and TSH. A clonidine-test failed to induce pituitary GH response. A corticotropin-releasing factor (CRF) provocative test was conducted after 6 months without the use of prednisone with a normal ACTH response after CRF in the affected sibling. Plasma IGF-I and IGF-BP3 were below normal levels. Serum E2 (females) and serum testosterone (males) levels were very low. MRI evaluation of the pituitary indicated pituitary aplasia in all subjects. The phenotype described in this kindred is different from families reported with Pit-1 mutations. However, it resembles previously published kindreds with similar clinical and biochemical findings. The relative preservation of ACTH suggests a genetic defect early in pituitary gland development.

Adolescent↗
PubMed1996

Triiodothyronine mimics the effects of estrogen in breast cancer cell lines.

MCF-7 (estrogen receptor positive--ER+) and MDA-MB-231 (estrogen receptor negative--ER-) are human breast cancer cell lines which express functional thyroid hormone receptors (c-erb A alpha1 and c-erb beta1) as indicated by stimulation of mitochondrial alpha-glycerophosphate dehydrogenase. In MCF-7, mimicking E2, T3 stimulated growth in a dose-dependent (10(10) M - 10(-8) M) manner, induced the expression of progesterone receptor and growth factor TGFalpha mRNAs and inhibited that of TGFbeta mRNA; T3 also increased progesterone binding and LDH5 isozyme activities. None of these effects were observed in (ER-) MDA-MB-231 cells. 10(-6) M tamoxifen (TAM) reverted growth stimulation, suppressed progesterone receptor and TGFalpha mRNA induction and restored TGFbeta mRNA to control levels in T3-treated MCF-7 cells. That T3 is acting in MCF-7 cells via its binding to ER is suggested by the immunoprecipitation of pre-bound 125I-T3 from MCF-7 nuclear extracts by an ER-specific monoclonal antibody and by the displacement of 3H-estradiol binding to ER by radioinert T3.

Breast Neoplasms↗
PubMed1994

Modulation of insulin secretion and 45Ca2+ efflux by dopamine in glucose-stimulated pancreatic islets.

1. The effect of dopamine on calcium efflux and insulin secretion is examined in the present study. For this purpose, islets isolated from adult Wistar rats were perfused or incubated at 37 degrees C for 60 min. 2. The results obtained from perfused islets indicate that 100 microM dopamine, in the presence of 5.6 mM glucose, increases insulin secretion and causes a modest elevation of 45Ca2+ efflux. However, glucose stimuli (from 5.6 to 16.7 mM) provoked an unexpected reduction of insulin release, with no alteration in calcium efflux, when 100 microM dopamine was present in the perfusion medium. 3. Similar findings were obtained in incubated islets when the prolonged effect of dopamine was investigated. 4. The observations described above led us to conclude that bioactive amines might play an important role in the modulation of the glucose-induced insulin secretion.

Animals↗
PubMed1992

Obesity is the major cause of alterations in insulin secretion and calcium fluxes by isolated islets from aged rats.

To investigate the alterations in insulin secretion induced by aging, 2-month-old, 12-month-old, and 12-month old lean rats (submitted to a caloric restriction during the last month that causes a weight loss of approximately 20%) were studied. As expected, glucose intolerance and increased insulin response were observed during IV-GTT in 12-month-old rats. These effects were, however, reversed by weight loss. Insulin secretion was investigated in isolated islets both during static incubation and perifusion. In 12-month-old rats insulin secretion and 45Ca2+ efflux were lower only in the second phase of the hormonal secretion, suggesting an involvement of voltage-sensitive calcium channels in these phenomena. Considering that in vivo and in vitro alterations were reversed after weight loss, it is possible to conclude that obesity is probably a major cause of impaired insulin secretion in 12-month-old albino rats. Since 14C-glucose metabolism was not changed in islets from aged rats, the effect of obesity on insulin secretion is not due to altered glucose metabolism in pancreatic B-cells.

Aging↗
PubMed1990

Insulin secretion in Walker 256 tumor cachexia.

The effect of cachexia on insulin secretion was examined in adult male rats. Isolated islets of Langerhans from Walker 256 tumor-bearing rats secreted less insulin by glucose stimuli as compared with the control group; this was accompanied by significant change in 45Ca2+ outflow rate. Reduced insulin secretion to glucose stimuli in tumor-bearing rats probably led to low insulinemia (one-third). These findings indicate that reduced insulin secretion is probably an important factor for the development of cachexia in Walker 256 tumor-bearing rats.

Animals↗
PubMedDate not supplied

Chromophobe renal cell carcinoma: clinicopathological study of 7 cases.

Chromophobe renal cell carcinoma (CRCC) may be grossly and microscopically confused with oncocytoma. It is now believed that many, if not all, of the so-called malignant oncocytomas or oncocytomas with metastases reported in the literature were indeed chromophobe renal cell carcinomas. CRCC is characteristically positive for colloidal iron and shows cytoplasmic microvesicles in electron microscopy. This study of CRCC is thought to be the first one done in Latin America. Of a total of 106 renal epithelial neoplasms, 7 (6.6%) fulfilled the criteria for chromophobe renal cell carcinoma. This frequency in Brazil is similar to that in other parts of the world. There was no difference in age, sex, and race distribution of CRCC compared to usual renal epithelial tumors. Grossly, the CRCC ranged in size from 3.5 to 20 cm (average: 10.2 cm) in greatest dimension. Most frequently, the tumor was brown on the cut surface. The growth pattern showed compact areas in all tumors and, in most of the cases, both clear and eosinophilic cellular subtypes were seen. The electron microscopic findings favor an origin of the microvesicles from outpouchings of the outer membrane of mitochondria. The strong positivity for colloidal iron in spite of the destruction of the cytoplasmic vesicles in paraffin-embedded specimens seems to indicate that the acid mucopolysaccharides are not located inside the microvesicles. By the time of diagnosis, only one case had regional lymph node metastases and this particular case was the only one mixed (associated with the usual renal cell carcinoma). The follow-up examination after nephrectomy showed that prognosis seems to be favorable in CRCC, except when the tumor coexists with the usual renal cell carcinoma.

Adenocarcinoma↗