Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

PIMA: A population informative multiplex for the Americas.

We describe an ancestry-informative autosomal SNP multiplex designed to be a small-scale, flexible panel that can complement uniparental markers in assessing the American variability (i.e. pre-Colombian) found in contemporary indigenous American populations. This study centered on choosing SNPs with the specific characteristics of: 1) extreme allele frequency differences between indigenous Americans and the African, European and East Asian population groups that contribute to present-day population variation in the Americas; 2) high informativeness-for-assignment In values; and 3) well-spaced genomic distribution and chromosomal separation from existing small-scale forensic ancestry marker sets. The resulting capillary electrophoresis SNaPshot single base extension test was named: PIMA (Population Informative Multiplex for the Americas), comprising 26 autosomal SNPs, a single X-chromosome SNP plus the amelogenin sex marker adapted for SNaPshot. PIMA complements the established 34plex forensic ancestry panel to provide a powerful and simple tool for the analysis of American populations, including those with admixed histories, commonly encountered in America. Comparing the results obtained with the combined marker panels of PIMA and 34plex to SNP data from a much larger ancestry panel allowed us to gauge their relative efficiency. PIMA+34plex gives equivalent power to the 314-SNP 'LACE' genomic ancestry control panel, while requiring a much smaller genotyping effort. The ancestry profiles and genetic structure of 22 populations spread across the American continent were estimated using PIMA+34plex data, and those estimates were contrasted with information provided by uniparental markers (mtDNA and Y-chromosome loci) for a small set of admixed individuals from Venezuela. Our results indicate that an American genetic component is efficiently detected in contemporary American populations using a small set of ancestry informative SNPs, and these co-ancestry estimates are consistent with the known history and demography of the Americas. The small scale and high population differentiation power of PIMA, particularly when combined with 34plex, provides a practical and powerful tool for genetic studies of American populations as well as forensic DNA analyses.

Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes.

The cytochrome P450 family (CYPs) and the glutathione S-transferase (GSTs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. In this study we examine the role of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk in Brazilian women. The study population consisted of 102 incident breast cancer cases and 102 healthy controls. Genotyping analyses were performed by PCR-based methods. A significant finding was observed between GSTP1 Ile-Val polymorphism and breast cancer risk (OR = 1.81; CI 95% = 1.04-3.16). A significant association was observed between women with 0-2 risk genotypes and those with 4 or more risk genotypes (OR = 2.42; CI 95% = 1.13-5.18) when the potential combined effects of the risk genotypes were examined. No significant differences between cases and controls were found correlating the genotypes and the clinical-histopathological parameters. In conclusion, in our population only GSTP1 was associated with breast cancer risk. However, when the genes were tested in combination, a significant association in the breast cancer risk was observed.

Prognostic significance of silent myocardial ischemia after a first uncomplicated myocardial infarction.

Forty asymptomatic patients were studied after a first uncomplicated myocardial infarction. They were 36 men and 4 women, with a mean age of 52.6 yr; the location of myocardial infarction was in the anterior wall in 18 (45%) patients and in the inferior wall in 22 (55%). The patients were submitted to: (1) 48-h Holter monitoring, during the 2nd and 8th weeks after the acute event; (2) exercise testing during the same periods; (3) cardiac catheterization and coronary arteriography. Patients with clinical conditions associated with cardiac rhythm disturbances or repolarization abnormalities were excluded. The electrocardiographic methods identified 11 (27.5%) patients with silent myocardial ischemia. Patients with and without silent ischemia were similar in relation to sex, age, coronary risk factors, arrhythmias, left ventricular function and follow-up. Patients with silent ischemia had more inferior wall myocardial infarctions, but the difference was not statistically significant. Patients with silent ischemia had significantly more extensive coronary artery disease (45.5% multivessel disease) when compared to those without ischemia (14.8% multivessel disease) (p < 0.05). After a 2-yr follow-up, 4 (36.4%) patients with and 1 (3.4%) without silent ischemia had a coronary event (p < 0.05). Kaplan-Meier analysis demonstrated a significantly higher cumulative probability of not experiencing a new coronary event for the patients without silent ischemia (96.5%) as compared to those with silent ischemia (62.3%) (p < 0.01). Our results suggest that silent myocardial ischemia after a first uncomplicated myocardial infarction carries an adverse prognosis and should be routinely investigated.

[Pseudoaneurysm of the left ventricle resected 20 years after acute myocardial infarction]. / Pseudoaneurisma do ventrículo esquerdo ressecado vinte anos após infarto agudo do miocárdio.

A 67 year-old-man suffered an uncomplicated myocardial infarction twenty years ago. By January 1990 an abnormal cardiac contour was noted on a chest radiography. Contrast ventriculography revealed a pseudoaneurysm of the left ventricle. The patient underwent open heart surgery and remains asymptomatic 12 months after surgery. This is the longest time interval between the myocardial infarction and successful surgery that has been reported.

[Hemodynamic variable analysis in patients with systemic arterial hypertension undergoing physical exercise]. / Análise das variáveis hemodinâmicas em pacientes com hipertensão arterial sistêmica submetidos ao exercício físico.

PURPOSE: To verify the exercise-induced hemodynamic changes in moderate hypertensive patients. METHODS: Twenty nine patients were studied and they were submitted to cycloergometer supine exercise (50w and 100w) during cardiac catheterization. The hemodynamic variables were measured: cardiac index (CI), stroke volume (SV), systemic arterial resistance (SAR), pulmonary arterial resistance (PAR), wedge pressure (WP), right atrial pressure (RA), systolic arterial pressure (SP), diastolic arterial pressure (DP), mean arterial pressure (MP) and heart rate (HR). To evaluate the cardiac function, the patients were divided in two groups: GI with CI > 2.5 ml/min/m2 and GII CI < 2.5 ml/min/m2. RESULTS: During exercise, patients from GI and GII were similar-according to MAP, RA, WP, and HR. On the other hand, GI and GII exhibited different (#) behavior regarding SV, PAR and SAR. During the three exercise conditions, rest (R), 50w and 100w it was observed: a) PAR-R = 50 = 100 (GI); b) MP, PAR, WP, SV, SAR-R #50 #100 (GI); c) HR, PAR and SAR-R #50 #100 (GII). There was no correlation between the cardiac function (CI, SV) and the circulatory adjustment (PAR and SAR) or the pressure curve (SP, DP, MP) and HR. CONCLUSION: The results suggest that the cardiac function of GI patients depends, mainly, on the inotropism, while in GII patients it depends on the decrease of the afterload (PAR and SAR). Those changes may appear even in the late exercise stage (100w), with a bias to attain the GI levels. Those observations suggest functional changes in vasomotor tone of GII patients.

[Variability of the heart rate and silent ischemia after myocardial infarction]. / Variabilidade da freqüência cardíaca e isquemia silenciosa após infarto do miocárdio.

PURPOSE: To show a possible relation between heart rate and silent myocardial ischemia. METHODS: Forty-nine ischemic episodes were registered in six patients during a total period of 576-hour Holter monitoring. Those patients were selected from a group of 40 asymptomatic individuals after a first uncomplicated myocardial infarction; 11 (27.5%) showed ischemia during daily activities or exercise, the six selected patients had myocardial ischemia on Holter monitoring. RESULTS: The silent episodes consisted 92% of the total ischemic burden; they lasted from 1 min 30 s to 20 min and the ST-segment depression varied from -1.1 mm to 3.3 mm. Thirty-five (72%) episodes occurred at rest or during light physical activities; nine (18.5%) occurred between 7:00 AM and 12:00 PM; eight (16.5%), between 12:00 PM and 6:00 PM; 17 (35%) between 6:00 PM and 12:00 AM and 15 (30%), between 12:00 AM and 7:00 AM. There was no significant change (more than 20%) in heart rate at the onset of ischemic episodes in relation to the heart rate 1 minute before (94.63 +/- 9.79 bpm and 99.47 +/- 10.99 bpm, respectively). Complex ventricular arrhythmias occurred in all patients and only one of them had an episode of nonsustained ventricular tachycardia related to silent ischemia. CONCLUSION: Our results suggest that there is no relation between heart rate, arrhythmias and silent ischemia.

[Severe pulmonary embolism in a single lung]. / Embolia pulmonar grave em pulmão único.

A 68 years old white man complaining of hemoptysis in the last 2 months was admitted for evaluation. He was a heavy smoker and thorax radiography as week as CT Scan showed a 5 cm mass in the right pulmonary hilum. Endoscopy with biopsy demonstrated an adenocarcinoma of middle lobe. He was operated on and a tumor was found in the middle lobe with invasion of the other two lobes and pericardium. A right pneumectomy was performed. In the 10th postoperative day the patient sustained a pulmonary thromboembolism. A pulmonary scintigraphy showed hypoperfusion of large areas of left lung. He was medically treated and had a good response. The patient was discharged in the 22nd postoperative day. Pulmonary thromboembolism in bowen more severe in patients with single lung, nevertheless the recovery of this patients was good with early diagnosis and treatment.

[The anatomical-functional characteristics of the pelvic floor and quality of life of women with stress urinary incontinence subjected to perineal exercises]. / Las características anatomofuncionales del suelo pélvico y la calidad de vida de mujeres con incontinencia urinaria de esfuerzo sometidas a ejercicios perineales.

OBJECTIVE: To determine the effects of exercise in anatomic abnormalities of the pelvic floor (SP) and the quality of life (QOL) of women with stress urinary incontinence (SUI). METHOD: An experimental study with 50 women with SUI, distributed randomly into two groups, experimental (GE, 49.24±7.37 years) and control group (CG; 45.25±5.60 years). The groups performed ultrasound evaluation of the SP, evidence of pelvic floor muscle strength by palpation bidigital, surface EMG motor activity and replied to the CV before and after treatment. The GE had 16 sessions of pelvic floor exercises twice a week for 30min. RESULTS: Comparison between the GE and GC revealed significant differences in favor of GE, namely: mobility of the bladder neck (Δ=-0.79mm, p=0.00), thickness of pelvic floor muscle (Δ=-0.04mm, p=0.00), EMG (Δ=0.05.V, p=0.00), muscle strength by the AFA (Δ=0.05 level, p=0.00), DOMI1 (Δ%=5.67%, p=0.00), DOMI2 (Δ%=18.00%, p=0.00), DOMI3 (Δ%=18.22%, p=0.00), DOMI4 (Δ%=4.45%, p=0.00), DOMI5 (Δ%=0.22%, p=0.00), DOMI6 (Δ%=2.00%, p=0.00), DOMI7 (Δ%=3.78%, p=0, 00), DOMI8 (Δ%=6.33%, p=0.00), DOMI9 (Δ%=4.03%, p=0.00). CONCLUSION: It was modified and improved anatomic features of the pelvic floor of women from GE through perineal exercises, which will positively influence the CV of these women.

Light and electron microscopic analysis of controlled injury to follicular unit grafts.

BACKGROUND: Careful manipulation of hair units is essential for a good yield of transplanted hair. OBJECTIVE: To analyze the morphology of dissected follicular units submitted to crushing, stretching, bending, and drying. METHODS: Follicular units were either crushed, bent, stretched with forceps, or left drying on surgical gloves for 3 minutes. The specimens were fixed and prepared for observation with light microscopy or transmission and scanning electron microscopy. RESULTS: No alterations were detected in follicular units that had been crushed, bent, or stretched. Major damage occurred in samples that were left to dry on gloves. CONCLUSION: Letting the follicular unit dry appears to be the worst mishandling to which the follicular units may be subjected during routine hair transplantation.

The Awá-Guajá Indians of the Brazilian Amazon. Demographic data, serum protein markers and blood groups.

The South-American Indian group Awá-Guajá, currently living in the State of Maranhão (Northeastern Brazil), is one of the most recently contacted Indian groups of the Brazilian Amazon. This group is made up by three partially isolated villages named Awá, Guajá and Juriti, and is characterized by having a young population, in which 47.6% of the individuals range from 0 to 14 years old. The sex ratios (male/female) for people of reproductive age are 1.13 for Awá village, 2.00 for Guajá, 3.33 for Juriti and 1.61 for the tribe as a whole. Fst and heterogeneity analysis show that, despite the small differences observed among villages for the eight genetic systems analyzed, the Awá-Guajá tribe is constituted of only one population. Furthermore, comparisons between Awá-Guajá and Urubú-Kaapor tribes indicate that they are still isolated genetically, in spite of the fact that they share territories.

Organization of intermediate filaments and their association with collagen-containing phagosomes in mouse decidual cells.

We have analyzed the distribution of intermediate filaments (IF) in the cytoplasm of mature decidual cells of mice. IF were scattered throughout the cytoplasm of these cells although there was a preferential accumulation around the nuclei. In many cells a large area of the cytoplasm was occupied by a rich network of IF that extended from the perinuclear region toward the cell surface. Thin bundles of IF crossed the cytoplasm without a preferential orientation. IF were also seen in close association with nuclear pore complexes, gap junctions, mitochondria, and lysosomes. A very developed network of IF surrounded phagosomes that contained collagen fibrils. Longitudinal and cross sections of these phagosomes showed a very close association of IF with the phagosome membrane.

Sera from chronic chagasic patients with complex cardiac arrhythmias depress electrogenesis and conduction in isolated rabbit hearts.

BACKGROUND: Immune dysfunction has long been proposed as a mechanism for the etiopathogenesis of the chronic phase of Chagas' disease. Antibodies of chagasic patients have been shown to interfere with electric and mechanical activity of embryonic myocardial cells in culture. Here, we demonstrate that antibodies derived from a group of chronic chagasic patients are able to induce disturbances in the electrogenesis and conduction in isolated adult rabbit hearts. METHODS AND RESULTS: Sera from chronic chagasic patients with complex cardiac arrhythmias (ChA+) decreased heart rate (from 131+/-26 to 98+/-37 bpm [mean+/-SD]; n=6; P<.05) in isolated rabbit hearts when perfused at a dilution of 1:100 (vol:vol) by the Langendorff method. Sera from another experimental group of four chronic chagasic patients without complex arrhythmias (ChA-) and two control groups composed of five Wolff-Parkinson-White (WPW) syndrome patients and five orthopedic surgery patients did not affect heart rate when tested under similar conditions. In addition, sera from five of six ChA+ patients and from one WPW patient induced AV conduction blockade. Effects of the sera from ChA+ patients are due to their IgG fractions. Both serum and IgG effects are blocked by atropine (10 micromol/L). CONCLUSIONS: Antibodies of ChA+ patients decrease heart rate and induce AV conduction block in isolated adult rabbit hearts through activation of muscarinic receptors.

Group-specific component (GC) in Curiaú and Pacoval, two African-derived Brazilian populations.

The group-specific component (GC) system is of interest in anthropological genetic studies because the distribution of its subtypes distinguishes among major ethnic groups. The GC system was analyzed in Curiaú and Pacoval, two remnant Quilombo populations (African-derived populations) from the Brazilian Amazon. There was no significant statistical difference in allelic frequencies between the two populations or between them and three other African-derived Brazilian populations (Mimbó, Sítio Velho, and Gaucinha in Northeastern Brazil). These populations share similarities among themselves and with African populations (high frequencies of GC*1F and lower frequencies of GC*1S), which may reflect the influence of a high level of African contribution to their formation, but there is a clear difference between them and Europeans and South American Indians. It is suggested that the GC system is a useful marker for studying relationships between single populations and major ethnic groups, but does not discriminate between populations which share the same parental stock.

Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens.

Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2beta. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.