Better predictive factors in endocrine-responsive breast cancer than the estrogen receptor itself.
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Biomedical subjects
Publications and source records attributed to S Braga.
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In this case report, the authors report the presence of two supposedly antagonic immune diseases in the same patient. The patient is a 45-year-old white woman with a history of asthma and allergic rhinitis for the last 10 years. Asthmatic symptoms were present and were triggered after exposure to dust and mold. Her Human T-Lymphotropic Virus Type I (HTLV-I) seropositive status was detected by chance five years ago during a routine screening for blood donation. Skin prick tests were positive for Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis. Cytokine levels in unstimulated cultures were: IFNgamma= 1195 pg/ ml, TNFalpha = 460 pg/ml, IL5 = 41 pg/ml and IL10 = 265 pg/ml.
BACKGROUND AND AIM: Total plasma homocysteine (tHcy) is an independent risk factor for cardiovascular diseases. Among other dietary and non-dietary factors, B vitamins, such as folate, riboflavin and cobalamin, are primary determinants of tHcy in the general population. However, research has concentrated on the relationship of these nutrients with tHcy, and little is known about overall eating patterns and tHcy. METHODS AND RESULTS: In this study, we analysed whether a diet score based on the consumption of folate-, riboflavin- and cobalamin-rich food groups was associated with tHcy in a sample of 140 institutionalised elderly subjects (59 men and 81 women aged 60-80 years) from Northern Spain. The food groups identified as the major contributors to the intake of the three vitamins were vegetables, fruit, fish, meat and milk and dairy products. The mean tHcy level was 13.3+/-5.1 micromol/L (range: 3.9-30.7 micromol/L). None of the food groups predicted tHcy levels individually, but the overall diet score was inversely associated with tHcy in a multiple linear regression analysis. High tHcy levels (>16 micromol/L) were almost twice as prevalent in the groups scoring less than 7 than in those scoring 7 or more (37.5 vs 19.6%, p=0.021). CONCLUSIONS: These data suggest that a dietary pattern characterised by high intakes of B vitamin-rich foods is associated with a lower tHcy concentration and a reduced percentage of high tHcy levels in elderly subjects. They also support the use of dietary pattern approaches to evaluate the relationships between diet and health outcomes that go beyond single nutrient analyses.
BACKGROUND: In spite of estrogen replacement therapy being extensively used in clinical and experimental studies without renal impairment, there are no long-term studies concerning estrogen replacement in chronic renal failure. METHODS: In this experimental study, six groups of nephrectomized and ovariectomized animals were treated with different doses of 17beta-estradiol, alone or in combination with calcitriol, to evaluate the effect of these treatments on bone metabolism. RESULTS: Biochemical results showed that estrogen alone did not have any effect neither on calcium nor on PTH serum levels. By contrast, in the groups treated with calcitriol, the levels of serum calcium were significantly higher, and the levels of iPTH were significantly lower than those observed in the control group. Animals receiving the combined treatment with estrogen and calcitriol showed the greater gain in uterus weight and a better bone mineral density at the lumbar site and the proximal and distal tibia sites. CONCLUSION: The combination of estrogen and calcitriol is the most effective therapy to prevent bone mass loss in animals with chronic renal failure and estrogen deprivation.
The modulation of the immune response has been used as therapy for clinical disorders associated with human T-lymphotropic virus type 1 (HTLV-1) infection. In this study, the cytokine profile was evaluated in 26 asymptomatic HTLV-1 blood donors. Additionally, both the cell responsible for producing interferon-gamma (IFN-gamma) and the role of exogenous interleukin (IL)-10 in downregulating IFN-gamma production were studied. Cytokine levels were determined in supernatants of unstimulated lymphocyte cultures by enzyme-linked immunosorbent assay. The levels of IFN-gamma, tumor necrosis factor-alpha, IL-5, and IL-10 were higher in supernatants of the lymphocyte cultures taken from HTLV-1-infected donors than in those taken from healthy subjects. Although depletion of CD8+ T cells and natural killer cells did not affect IFN-gamma production, depletion of CD4+ T cells significantly decreased IFN-gamma production. Furthermore, at a concentration of 2 ng/ml, IL-10 had only a minimum effect on IFN-gamma production, although at high concentrations (100 ng/ml), IL-10 decreased IFN-gamma production by 50% in HTLV-1-infected individuals. These data indicate that both T helper 1 and T helper 2 cytokines are elevated in HTLV-1 infection and that IL-10 in high concentrations modulates IFN-gamma production in these patients.
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BACKGROUND: Aluminium overload leads to parathyroid hormone (PTH) suppression. However, it is unclear whether a decrease in synthesis or release of the hormone is mainly involved. The aim of this study was to assess the effect of an acute administration of aluminium on PTH synthesis and release in rats with chronic renal failure and secondary hyperparathyroidism. METHODS: The study was performed using 100 adult male Wistar rats (body weight 443+/-54 g). 7/8 nephrectomy was performed and the rats were maintained on a high dietary phosphorous intake. Five weeks after surgery, the rats were randomly divided into two groups, one loaded with aluminium (AlCl3) and the other given placebo. Aluminium or placebo were administered i.p. for two consecutive days. The placebo group received saline at the same pH as the aluminium solution. After 2 weeks, serum calcium, phosphorous, creatinine, PTH, and aluminium were measured. The parathyroid glands were removed and PTH messenger RNA (mRNA) was measured by northern blot. Intact PTH was measured by IRMA (Rat PTH, Nichols Institute). RESULTS: No differences in serum PTH levels were found between the two groups after 5 weeks of renal failure. At the end of the study the rats given aluminium had higher aluminium levels than the placebo group and lower PTH levels. No significant differences were found for calcium, phosphorous, renal function, or body weight. PTH mRNA expression was lower in the aluminium group than in the placebo group. CONCLUSION: The administration of aluminium in rats with chronic renal failure resulted in reductions in serum PTH and PTH mRNA. Thus far, previous studies had demonstrated that aluminium suppressed PTH release. The present findings suggest that PTH synthesis is also reduced.
The D allele at the angiotensin-I-converting enzyme (ACE)-insertion/deletion polymorphism has been associated with an increased risk of developing several pathological processes, such as coronary heart disease and ventricular hypertrophy. Individuals with the DD genotype show a significantly increased left-ventricular mass in response to physical training, compared to the II genotype (which would be associated with the lowest plasma ACE levels) and the ID genotype. The II genotype has been linked to a greater anabolic response. In accordance with a role for ACE in the response to rigorous physical training, a higher frequency of the I allele has been reported to exist among elite rowers and high-altitude mountaineers. Sixty elite (professional) athletes (25 cyclists, 20 long-distance runners, and 15 handball players), and 400 healthy controls were genotyped for the DNA polymorphisms of the ACE, angiotensinogen (Ang) and angiotensin receptor type 1 (AT1) genes. Plasma ACE levels showed a strong correlation with the I/D genotype in our population. The I-allele occurred at a significantly higher frequency in athletes compared to controls (P = 0.0009). Gene and genotype frequencies for the Ang and AT1 polymorphisms did not differ between athletes and controls. Since the frequency of the ACE I allele was significantly increased among our elite athletes, we conclude that the ACE polymorphism represents a genetic factor that contributes to the development of an elite athlete.
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BACKGROUND: Antiperinuclear factor (APF) is an autoantibody directed against (pro)-filaggrin molecules. OBJECTIVE: We evaluated whether APF determination is useful for the diagnosis of psoriatic arthritis (PA). METHODS: We determined APF titers in sera from patients with PA (n = 76), psoriasis vulgaris (n = 38), noninflammatory rheumatic diseases (NIRDs, n = 119), rheumatoid arthritis (RA, n = 159) both with negative (n = 36) and positive (n = 123) rheumatoid factor (RF) tests, as well as from 204 healthy controls. We used an indirect immunofluorescence test on epithelial cells from human buccal mucosa as a substrate. RESULTS: In patients with PA, 7.9% of the serum samples were APF-positive. The incidence was greater than in healthy controls (1.0%; P < .01), similar to those with uncomplicated psoriasis (2.6%; P = NS) and NIRDs (4.0%; P = NS), and lower than in RF-negative (52.7%; P < .001) and RF-positive (90.2%; P < .001) patients with RA. Three APF-positive patients with PA had symmetric joint involvement and 3 had pustulotic arthroosteitis. CONCLUSION: The APF test may be useful in differentiating PA from RA, and APF may be specific for two PA subgroups.
OBJECTIVE: To determine the predictive value of lipoproteins for early coronary heart disease in men less than 50 years old from southern Europe. METHODS AND RESULTS: One hundred and fifty-seven men less than 50 years old were consecutively evaluated for symptoms of coronary heart disease in a tertiary referral hospital. A group of 415 male miners with mean age of 41 +/- 8 years without clinical or electrocardiographic evidence of coronary disease served as controls. Blood samples were taken by venipuncture as soon as possible after admission to the hospital from cases and after 12 hours of fasting in controls. Plasma concentrations of total cholesterol (TChol), HDL-cholesterol (HDLChol), triglycerides (TG), apoproteins A1 and B and Lp(a) were determined. The odds ratios, as estimators of relative risk, were computed using the Mantel-Haenszel procedure. The odds ratios from highest to lowest were a TChol/HDLChol ratio equal to or greater than 5: 10.7 (95% confidence interval (CI) 6.1 to 18.8), TG > 2.25 mmol.l-1 and HDLChol < 0.9 mmol.l-1: 7.4 (95% CI 3.9 to 14.1), HDLChol < 0.9 mmol.l-1: 6.9 (95% CI 4.5 to 10.6), TG > 2.25 mmol.l-1: 3.3 (95% CI 2.0 to 5.3), Lp(a) > 30 mg.dl-1: 2.7 (95% CI 1.8 to 4.1), Apo B > 120 mg.dl-1: 2.4 (95% CI 1.3 to 4.2), non-HDLChol > 5.2 mmol.l-1: 2.2 (CI 1.4 to 3.3), TChol > 6.5 mmol.l-1: 1 (95% CI 0.6 to 1.6), TChol > 5.2 mmol.l-1: 0.9 (95% CI 0.6 to 1.3). CONCLUSIONS: This study indicates that in males less than 50 years a ratio TChol/HDLChol > or = 5 presents the greatest risk power for early coronary heart disease. Plasma concentrations of TChol alone did not demonstrate to have value as risk factor for cardiovascular disease.
The nature of changes in the lipid profile caused by an acute infection is controversial. The aims of the present study were to study the changes in plasma lipids and lipoproteins in community-acquired pneumonia, to determine whether these changes differ according to the aetiologica/agents, and finally to observe the behaviour of these lipoproteins six months later. Sixty patients, aged between 18 and 87 years, admitted during the period September 1992 and April 1993 with suspected community-acquired pneumonia, were included in the study. Fifty-three of the patients completed the 15-day follow-up investigation, and 37 remained available for study for up to 6 months. On admission and at 15 and 180 days, analyses were carried out for total cholesterol, HDL cholesterol, apolipoproteins A1 and B, triacylglycerols and transaminases. Student's t test for parametric variables was used for statistical analysis, and the Mann-Whitney test for non-parametric variables. The concentrations of total cholesterol (4.2 +/- 1.0 vs 5.5 +/- 1.3 mmol/1), HDL cholesterol (0.9 +/- 0.4 vs 1.2 +/- 0.3 mmol/l), apolipoprotein A1 (0.80 +/- 0.25 vs 1.15 +/- 0.28 g/l) and apolipoprotein B (0.77 +/- 0.28 vs 0.95 +/- 0.28 g/l) showed significantly lower values during the acute infectious process. These analyte concentrations became stable after 15 days with the exception of HDL cholesterol which continued to increase until 6 months (1.2 +/- 0.3 vs 1.3 +/- 0.3 mmol/l, p < 0.01). Patients with non-viral atypical pneumonia showed, on admission, higher triacylglycerol values (1.8 +/- 0.8 vs 1.3 +/- 0.9 mmol/l, p < 0.01) and lower HDL cholesterol values (0.6 +/- 0.3 vs 1.0 +/- 0.4 mmol/l, p < 0.03). Values of aspartate aminotransferase (112 +/- 117 vs 23 +/- 11 U/l, p < 0.001), alanine aminotransferase (127 +/- 141 vs 24 +/- 16 U/l, p < 0.02) and gamma-glutamyl transferase (113 +/- 158 vs 33 +/- 25 U/l, p < 0.03) were higher in the subgroup of non-viral atypical pneumonia. In conclusion, patients with community-acquired pneumonia present a significant decline in total cholesterol, HDL cholesterol and apolipoprotein A1 and B concentrations. Lower concentrations of HDL cholesterol are maintained up 15 days. Patients with non-viral atypical pneumonia present on admission significantly higher triacylglycerol and lower HDL cholesterol values. Those with non-viral atypical pneumonia also present higher transaminase values.
Lipoprotein(a) [Lp(a)] had been shown to be a strong independent risk factor for ischaemic heart disease. Our aim was to investigate the relationships between Lp(a) and other cardiovascular risk factors. 423 male miners (age 40 +/- 8 years) were analysed according to the following variables: age, arterial blood pressure, alcohol and cigarette consumption, total cholesterol and Lp(a). Analysis of the data was performed using the Kruskal-Wallis and Spearman tests. Analysis of variance showed statistical differences in Lp(a) levels with cigarette consumption (p < 0.02) and age (p < 0.001). No differences with corrected total cholesterol, blood pressure and alcohol consumption were found. Lp(a) and total cholesterol were correlated (p < 0.0001), but after correction for the estimated contribution of Lp(a) cholesterol this significant correlation disappeared. We conclude that male smokers have significantly lower Lp(a) values than non-smokers and those who quit. Our findings suggest that cigarette consumption is a probable environmental factor that might influence Lp(a) levels.
OBJECTIVE: To assess the diagnostic and prognostic power of antiperinuclear factor (APF) and to identify a specific pattern of rheumatoid arthritis (RA) of different evolution and prognosis. METHODS: One hundred and fifty-nine sera from patients with RA, 280 sera from patients with other rheumatic diseases and 204 sera from healthy subjects were examined for APF. RESULTS: Sensitivity and specificity of the test were, respectively, 0.82 and 0.99 when 1:80 serum dilution was considered positive but 0.84 and 0.92 when tested at the currently used 1:5 serum dilution. According to the data obtained from APF and rheumatoid factor (RF) testing, patients with RA were subdivided in 4 groups. Clinical and demographic features for each group were analyzed. RF+ and/or APF+ patients showed a common pattern of disease, whereas RF-/APF- patients showed fewer extraarticular manifestations (p < 0.02) including Sjögren's syndrome (p < 0.04) and an unusual onset of the disease characterized by an involvement of large joints (p < 0.0001). Higher titer of APF was detected at the onset of the disease than in longstanding RA (p < 0.02). CONCLUSIONS: APF is a valuable diagnostic tool and a useful additional marker for RA. 1:80 serum dilution allows more specificity without substantial loss of sensitivity. A specific pattern of RA can be identified on the basis of APF status.
OBJECTIVE: Different sets of diagnostic criteria have been proposed for Sjögren's syndrome (SS), but none have been validated with a large series of patients or in a multicenter study. We conducted the present study involving 26 centers from 12 countries (11 in Europe, plus Israel), with the goals of reaching a consensus on the diagnostic procedures for SS and defining classification criteria to be used in epidemiologic surveys and adopted by the scientific community. METHODS: The study protocol was subdivided into two parts. For part I, questionnaires regarding both ocular and oral involvement were developed; they included 13 questions and 7 questions, respectively. For part II a limited set of diagnostic tests was selected, and the exact procedure to be followed in performing these tests was defined. Part I of the study included 240 patients with primary SS and 240 age- and sex-matched controls. Two hundred forty-six patients with primary SS, 201 with secondary SS, 113 with connective tissue diseases but without associated SS, and 133 control patients were studied in part II. RESULTS: The study resulted in (a) the validation of a simple 6-item questionnaire for determination of dry eyes and dry mouth, which showed good discriminant power between patients and controls, to be used in the initial screening for sicca syndrome; and (b) the definition of a new set of criteria for the classification of SS. The sensitivity and specificity of the criteria in correctly identifying patients with either the primary or the secondary variant of SS were also determined. CONCLUSION: Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway.
The X-linked recessive centronuclear/myotubular myopathy (XLR-CNM/MTM1), a severe neonatal disorder characterized by generalized hypotonia, muscle weakness, and primary asphyxia, has recently been mapped to Xq28. This report presents the first four prenatal diagnoses of XLR-CNM using DNA markers of the Xq28 region. The analyses of one female and three male fetuses revealed maternal transmission of the XLR-CNM-associated alleles in all four cases. Two of the male fetuses have been aborted, and the pregnancies of the third male and the female fetuses have been continued. The diagnosis of XLR-CNM at the birth of the third boy, as well as the pathologic findings in the muscle of one of the aborted fetuses, confirmed the linkage results of the prenatal analyses. Our findings prove the DNA markers St14, cpX67, DX13, and pSt35-691 to be useful in prenatal diagnosis of XLR-CNM and present the possibility to confirm the diagnosis by histologic examination of the first-trimester abortus. This permits an indirect prenatal diagnosis of XLR-CNM in chorionic villus biopsies at 9 to 12 wk gestation, using DNA-based linkage analyses allowing early termination of an affected pregnancy.
Chronic renal failure (CRF) in rats (surgical nephrectomy, 5/6) as well as its derived bone lesions have been studied. Eighty-five male Wistar rats were used, to which chronic renal failure was induced in 1 or 2 surgical times, the parameters of renal function in basal conditions and at different times after surgery being determined. With the method used chronic renal failure is induced with values of creatinine clearance 2/3 times lower than the initial ones (p < 0.05), which stabilize at the 7th week. On the other hand the parathyroid hormone levels (PTH) in serum triple (from 125 +/- 49 to 395 +/- 191, p < 0.05), and a decrease in the tubular phosphate reabsorption is produced (p < 0.001). In bone histology an increase in resorption and bone formation is observed as well as paratrabecular fibrosis, all of which is compatible with the histological diagnosis of hyperparathyroidism. The model of surgical renal insufficiency with ablation of 5/6 of the renal mass, reduces renal function to 1/3 of the initial values after 7 weeks, this procedure having a 20% global mortality without differences being observed between the carrying out of nephrectomies in 1 or 2 surgical times. This degree of CRF was accompanied by secondary hyperparathyroidism both at the biochemical and histological levels, findings which are of great usefulness for future experimental studies.
Serum levels of the soluble form of the interleukin-2 receptor (sIL-2R) were measured in the sera of 32 patients with systemic lupus erythematosus. A significant correlation was observed between the levels of sIL-2R and the SLAM score of disease activity (R:0.40; p: less than 0.05). The correlation was slightly lower than those between the SLAM score and the levels of anti-dsDNA or of the complement activity. The levels of sIL-2R were not significantly correlated with those of serum anti-ds-DNA and complement, nor with a sign of peripheral blood B cell hyperactivity, such as the spontaneous in vitro production of anti-DNA antibodies.