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Biomedical subjects

C Lopes

Publications and source records attributed to C Lopes.

At least 37 records · Page 2Linked to original sources

Genetical analysis of visual system disorganizer (vid), a new gene involved in normal development of eye and optic lobe of the brain in Drosophila melanogaster.

A neuroanatomical screening of a collection of P-element mutagenized flies has been carried out with the aim of finding new mutants affecting the optic lobe of the adult brain in Drosophila melanogaster. We have identified a new gene that is involved in the development of the adult axon array in the optic ganglia and in the ommatidia assembly. We have named this locus visual system disorganizer (vid). Reversional mutagenesis demonstrated that the vid mutant was the result of a P-element insertion in the Drosophila genome and allowed us to generate independent alleles, some of which resulted in semilethality, like the vid original mutant, while the others were completely lethal. A genetic somatic mosaic analysis indicated that the vid gene is required in the eye for its normal development by inductive effects. This analysis also suggests an inductive effect of the vid gene on the distal portion of the optic lobe, particularly the lamina and the first optic chiasma. Moreover, the absence of mutant phenotype in the proximal region of the optic ganglia, including the medulla, the second optic chiasma, and the lobula complex underlying mosaic eyes, is suggestive of an autonomously acting mechanism of the vid gene in the optic lobe. The complete or partial lethality generated by different mutations at the vid locus suggests that this gene's role may not be limited to the visual system, but may also affect a vital function during Drosophila development.

Animals↗

Interaction between polyalkylcyanoacrylate nanoparticles and peritoneal macrophages: MTT metabolism, NBT reduction, and NO production.

PURPOSE: The nature of interactions between macrophages and drug carriers is of primordial importance either in the design of more effective therapeutic strategies for macrophage-associated pathogenesis or in establishing new approaches for pharmacological action avoiding macrophages. METHODS: Polyalkylcyanoacrylate nanoparticles (PMCA, PECA, PBCA and PIBCA nanoparticles) were assayed for their toxicity on peritoneal resident and thioglycolate-elicited macrophages. Cellular viability was assessed by MTT tetrazolium salt assay, oxidative burst by NBT reduction and NO production by nitrite evaluation. RESULTS: The nanoparticles tested led to cellular morphological modifications and induced toxicity in both types of macrophages in culture. The polyalkylcyanoacrylate nanoparticles uptake by peritoneal macrophages caused an increase in respiratory burst, as assessed by the NBT reduction assay, and induced the release of soluble toxic factors to the culture medium. The association of LPS with the PMCA nanoparticles significantly stimulated the production of nitric oxide (NO) by resident macrophages. In contrast, the association of PBCA nanoparticles with LPS does not increase the nitrite production as compared with LPS alone, which may be due to a different physico-chemical interaction between LPS and the two types of polymers. CONCLUSIONS: In cultured mice peritoneal macrophages, nanoparticles of PACA induce the production of oxygen reactive products, which cause changes in the cell metabolism of both resident and elicited macrophages. PMCA nanoparticles in association with LPS significantly increase the expression of the inducible isoform of nitric oxide synthase, leading to the release of large amount of NO, which may be highly cytotoxic to the cultured cells in the presence of peroxide generated from the oxidative burst.

Animals↗

Circadian rhythm in experimental granulomatous inflammation is modulated by melatonin.

Biological rhythms are detected in a variety of physiological and pathological conditions in man and animals, such as rheumatoid arthritis and asthma. Here we describe a circadian rhythm in experimental infectious and non-infectious granuloma. After 30 days of BCG (Bacillus Calmette-Guerin) or nystatin inoculation in the left hind foot of C57B1/6 mice, there is an oscillation with a period of approximately 24 hr in the variation of paw thickness, indicating a circadian rhythm. The acrophase occurred during the light phase, between 9:00 and 13:00 hr, while the nadir occurred in the dark phase, between 21:00 and 01:00 hr. The vascular permeability around the granulomatous lesions was higher at 12:00 hr than at 24:00 hr. This is in agreement with the observation that the thickness of a paw with granulomatous lesion is larger during the light phase. This rhythmic variation was eliminated by either pinealectomy or superior cervical ganglionectomy, which greatly reduce melatonin levels in the blood. Nocturnal replacement of melatonin in pinealectomized mice led to the re-establishment of the circadian rhythm. Thus, the rhythm of the granulomatous lesion is due to the rhythmic melatonin release by the pineal gland. This approach opens new questions regarding the modulation of chronic inflammation in inflammatory diseases that present rhythmic symptoms throughout the day.

Animals↗

Analysis of period circadian expression in the Drosophila head by in situ hybridization.

The expression of the period (per) gene of Drosophila melanogaster has been studied by in situ hybridization in the adult's head, where it is required for the fly to exhibit behavioral circadian rhythms. We have used non-radioactive in situ hybridization to obtain a high sensitivity and specificity on head sections, with single cell resolution. Consistent with previous per protein- or per reporter gene-expression, per-expressing cells were detected in the optic lobes and the central brain, as well as in the head sensory organs: eyes, ocelli, maxillary palps and proboscis. In the brain and the eyes, circadian fluctuations of the per mRNA abundance were observed in different per expressing cells.

Animals↗

[Prevalence, knowledge, treatment and control of arterial hypertension in Oporto, Portugal].

The aim of this study was to assess the prevalence, awareness, treatment and control of hypertension among subjects above the age of 39 years living in the urban area of Oporto, Portugal. One hundred and seventy seven individuals from the community were selected by random digit dialing. Each subject was asked about his/her personal history of hypertension, antihypertensive treatment and had his/her blood pressure measured. The prevalence of hypertension was 57.1%, defined by systolic blood pressure (SBP) > or = 140 mm Hg and/or diastolic blood pressure (DBP) > or = 90 mm Hg and/or administration of current the antihypertensive medication. If the values defining hypertension were SBP > or = 160 mm Hg, and DBP > or = 95 mm Hg the prevalence would be 37.9%. The overall prevalence of hypertension was higher in females, but a slightly higher non significant value was found in males in the fifth and sixth decades. Among hypertensives, 62.7% were aware of their condition, 56.7% were treated, 84.2% of hypertensives treated were controlled (SBP < 160 mm Hg and DBP < 95 mm Hg) and 44.7% were very well controlled (SBP < 140 mm Hg and DBP < 90 mm Hg). The question "Are you hypertensive?" had a sensitivity of 62.7%, a specificity of 83.6% and an accuracy of 75.7%. In the preliminary results of this study of an urban population with a high prevalence of hypertension, the awareness of hypertension is similar to that described in the United States of America twenty years ago, the percentage of hypertensives treated is similar to the American percentage fifteen years ago and the percentage of hypertensives treated and controlled is close to the current American percentage.

Adult↗

[Risk factors for myocardial infarct: a case-control study in Oporto, Portugal].

A case-control study of coronary heart disease (CHD) was conducted in Oporto, Portugal. The cases series consisted of 100 consecutive patients with first time acute myocardial infarction who were admitted to the Coronary and Intermediate Care Units of a major teaching hospital. The community controls were 198 individuals without evidence of CHD by the Rose questionnaire and electrocardiography, selected by random digit dialing, with a participation rate of 70%. Data was collected by trained interviewers using a structured questionnaire and blood samples were obtained for selected laboratory data. The main analysis was made through unconditional logistic regression with calculations of odds ratios (OR). Age, OR: 1.5 (95% CI: 0.8-2.9), male gender, OR: 6.7 (3.6-12.3), family history of premature CHD, OR: 2.4 (1.4-4.3), diabetes, OR: 3.4 (1.6-7.4), antecedents of hypertension, OR:1.9 (1.1-3.1), history of high cholesterol levels, OR: 2.3 (1.4-3.9), high levels of physical activity, OR: 2.0 (0.9-4.1) and tobacco smoking, OR: 8.3 (3.8-18.5) were significant risk factors of acute myocardial infarction. After controlling for demographic variables and for the mutual confounding effects of the risk factors, the investigated factors that remained significantly associated with the risk of developing acute myocardial infarction were male gender, OR: 17.3 (4.8-62.3), family history of CHD, OR: 3.6 (1.4-9.6), diabetes, OR: 4.2 (1.0-18.1), high cholesterol levels OR: 2.7 (1.2-6.1) and smoking habits, OR: 7.7 (1.8-32.4). A negative association with high education levels was significant after controlling for all the variables, OR: 0.01 (0.01-0.5).

Adult↗

Treatment of onchocerciasis.

Onchocerciasis ('river blindness') has for several centuries been the scourge of people living in certain areas of the world where the disease is endemic. The treatment available up to 10 years ago, diethylcarbamazine, had very severe secondary effects. The availability of ivermectin--a well tolerated and highly effective microfilaricidal drug--has completely changed this scenario. Ivermectin is now considered to be the drug of choice for the treatment of onchocerciasis. The prognosis for people with onchocerciasis has changed greatly. It is now possible to avoid the heavy infection loads seen previously, and patients, especially expatriates, may have their symptoms relieved by treatment. Ivermectin, used in mass treatment, may also improve the epidemiological situation, reducing the level of microfilariae in the skin of infected people and thus reducing the source for vector infestation. However, the treatment has to be repeated because the drug has no macrofilaricidal effect. Research today is focused on the finding of a drug able to destroy the adult worms that go on producing microfilariae for the length of their lives.

Animals↗

[Correlation between aortic transvalvular gradient obtained with Doppler ultrasonography and with hemodynamics study. Role of the underlying etiology].

In aortic stenosis, a good correlation was found between the gradients obtained by catheterization and Echo-Doppler. However, the correlation of these two methods in subgroups of patients with different etiologies of aortic stenosis is unknown. The aim of this study was to evaluate, whether the correlation between catheterization and Echo-Doppler was similar in patients with different etiologies of aortic stenosis. Patients with concomitant valvular disease were excluded. Only patients with a clearly defined etiology (based on clinical history, echocardiography, angiography and/or pathology) were included in this study. We evaluated 106 patients with aortic stenosis. Forty-nine patients had degenerative aortic stenosis, 32 bicuspid aortic stenosis and 25 rheumatic aortic stenosis. The percentage of male patients in each group were as follows: 57.1% in the denerative aortic group; 62.5% in the bicuspid aortic stenosis group; and 76% in the rheumatic aortic stenosis group. Mean age (years) was 69 +/- 6.7 in the degenerative aortic stenosis group, 58.1 +/- 7.5 in the bicuspid aortic stenosis group, and 64 +/- 7.1 in the rheumatic aortic stenosis group. In our study we found different correlations between the gradients obtained by the two methods-catheterization and Eco-Doppler-among the patients with different etiologies of aortic stenosis. The correlation coefficient (r2) was 0.54 (p < 0.001) in the rheumatic aortic stenosis group, 0.37 (p < 0.001) in the bicuspid aortic stenosis group and 0.21 (p = 0.001) in the degenerative aortic stenosis group. In conclusion, a good overall correlation was found between the two methods in aortic stenosis, however, this correlation is different in the three etiologies of aortic stenosis. The correlation is better in rheumatic valves, intermediate in bicuspid valves, and worse in degenerative valves. Changes in aortic valve morphology in these subgroups of patients are probably responsible for these different results.

Aged↗

Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development.

Many features of Down syndrome might result from the overdosage of only a few genes located in a critical region of chromosome 21. To search for these genes, cosmids mapping in this region were isolated and used for trapping exons. One of the trapped exons obtained has a sequence very similar to part of the Drosophila single-minded (sim) gene, a master regulator of the early development of the fly central nervous system midline. Mapping data indicated that this exonic sequence is only present in the Down syndrome-critical region in the human genome. Hybridization of this exonic sequence with human fetal kidney poly(A)+ RNA revealed two transcripts of 6 and 4.3 kb. In situ hybridization of a probe derived from this exon with human and rat fetuses showed that the corresponding gene is expressed during early fetal life in the central nervous system and in other tissues, including the facial, skull, palate, and vertebra primordia. The expression pattern of this gene suggests that it might be involved in the pathogenesis of some of the morphological features and brain anomalies observed in Down syndrome.

Amino Acid Sequence↗

p53 protein expression and nuclear DNA content in breast intraductal proliferations.

Immunohistochemical analysis of the p53 gene protein and cytometric assessment of nuclear DNA were performed in a series of 51 cases of intraductal breast proliferation. The series included 22 cases of intraductal hyperplasia without atypia, 6 cases of intraductal hyperplasia with atypia, and 23 cases of pure intraductal carcinoma. Expression of p53 protein was detected in one case of intraductal hyperplasia without atypia (4.5 per cent), one case of intraductal hyperplasia with atypia (16.6 per cent) and six cases of intraductal carcinoma (26.0 per cent). No significant correlation was observed between p53 expression and histological subtype of intraductal carcinoma. Aneuploidy was demonstrated in two cases of intraductal hyperplasia with atypia (33.3 per cent) and in 18 cases of intraductal carcinoma (78.2 per cent). All cases of intraductal hyperplasia without atypia were euploid. No significant association was observed between p53 protein expression and ploidy in intraductal hyperplasia. The only case of intraductal hyperplasia without atypia positive for p53 was euploid, whereas the only p53-positive case of intraductal hyperplasia with atypia was aneuploid. Among the intraductal carcinomas, only the aneuploid cases showed positivity for p53, regardless of histological subtype. The results suggest that some of the changes observed in invasive breast carcinoma, such as p53 expression and aneuploidy, are already present in breast intraductal proliferation, especially in areas with atypia and in intraductal carcinoma. The expression of p53 in breast intraductal proliferation may reflect the acquisition of p53 gene mutations in cells unable adequately to repair DNA damage, with genomic instability which would lead to clonal expansion and putative evolution to invasive disease.

Breast↗

Empirical development of brief smoking prevention videotapes which target African-American adolescents.

Two studies are described which provide evaluations for two brief videotapes developed as supplemental materials in the prevention of tobacco use among African-American adolescents. One videotape (the "soap opera") provides a more general audience-oriented presentation of prevention material and it was filmed primarily at a shopping mall, whereas the other videotape (the "rap") provides a "hip-hop generation" presentation, and it was filmed primarily at an outdoor hangout. The first study compared the two videotapes against each other. The second study compared the two videotapes combined in the same presentation, controlling for order of presentation, against a discussion group control. The results of the two studies indicated few differences in receptivity to the two videotapes among primarily African-American and Latino young adolescents. The rap videotape was rated as more accurate in its depiction of the African-American lifestyle, although both videotapes were equally liked. When shown together, the videotapes were not found to be superior in decreasing behavioral intention to smoke compared to a discussion group control. No change in trial of smoking was observed within or across conditions measured over a pre-post summer interval. These data suggest that "culturally sensitive" videotapes have no more of a short-term effect on youth than do other types of brief interventions which involve minority implementers.

Adolescent↗

[The Bland-White-Garland syndrome or an anomalous origin of the left coronary from the pulmonary artery. Apropos a case of a continuous murmur in an adult].

The authors report a case of anomalous origin of the left coronary artery from the trunk of pulmonary artery in an adult without significant symptoms, diagnosed by the presence of a continuous thoracic murmur. Because its low incidence and great mortality in the beginning of life, the appearance in the adult is extremely uncommon, especially without symptoms of cardiac failure, angina pectoris or myocardial infarction. In the present case, the patient was asymptomatic and was submitted to various echocardiograms before the diagnosis was suspected and confirmed with angiography. Surgical treatment was performed successfully with reimplantation of the anomalous vessel in the aorta.

Adult↗

[Growth and development of children with low birth weight at their first birthday].

The aim of this prospective study was to evaluate the effect of low birthweight on growth and development at one year of age, in a cohort of infants born between March 1992 and March 1993 at Hospital de Famalicão. Information was obtained from 199 children, 89 low birthweight cases and 110 born with a normal (> or = 2500 g) weight. The infant mortality rate (56 vs 9 per 1000), the frequency of growth (32% vs 4%, p = 0.0000003) or developmental delay (30% vs 11%, p = 0.002) were significantly higher in low birthweight babies. However, all cases of developmental delay corresponded to minor impairments. At age one, children born with a normal weight presented mean higher values for weight (10.0 +/- 1.1 kg vs 9.2 +/- 1.2 kg; p = 0.000005), length (74.2 +/- 7.1 cm vs 72.9 +/- 3.1 cm, p = 0.0006) and head circumference (46.4 +/- 1.9 cm vs 45.8 +/- 1.6 cm; p = 0.004). Prenatal characteristics such as the planning of the pregnancy, gestational birth weight, diseases during the pregnancy, gestational age or twining, significantly affected development at one year of age, showing that delays can be prevented before a child is born. In addition, post-natal exposures, such as home conditions, energy and nutrient intake, or coping with vaccination schedules and the occurrence of diseases during the neonatal and post-neonatal periods were significantly associated to developmental delay.(ABSTRACT TRUNCATED AT 250 WORDS)

Child Development↗

[Diffuse alveolar hemorrhage secondary to oral anticoagulant use].

We report a case of alveolar haemorrhage in all probability, attributable to the use of anti-vitamin K. The favourable outcome of this type of disease has rarely been reported with anticoagulants and fibrinolytics, most frequently in a disturbed haematological setting with disseminated intravascular coagulation or profound thrombocytopaenia. One should not forget this diagnosis in cases of acute respiratory failure in association with an alveolar syndrome in an exposed patient due to the fact that the outcome is generally favourable after correcting the disturbed coagulation.

Administration, Oral↗

[Nutrition and bone mineral density in premenopausal women].

Environmental factors have an important role in osteoporosis. Diet and, in particular, nutrients like calcium, vitamin D or phosphorus were extensively studied as determinants of bone mineral density, but the results remain conflicting and there is no clear evidence for an independent effect of such factors in the bone density of premenopausal women. We studied 66 healthy premenopausal women (20-40 years-old) aiming to relate bone mineral density, as measured in three different sites (distal forearm, lumbar spine and femoral neck) using single X ray and dual energy X-ray absorptiometry, with nutritional intake as estimated by a semi-quantitative food frequency questionnaire. Demographic, anthropometric and other life style variables were also assessed. There was a significant correlation between distal forearm and femoral neck (r = 0.57) or lumbar spine (r = 0.45) bone mineral density. No significant effect of age was observed for distal forearm bone mineral density in these women. In a stepwise multiple linear regression model, evaluating the contribution of all the variables studied, only body mass index (p=0.038) and vitamin A ingestion (p = 0.020) had an independent contribution for the variation in distal forearm bone mineral density. Mean bone mineral density, assessed in the femoral neck (p = 0.003) or the lumbar spine (p = 0.056) was different across tertiles of alcohol ingestion, being higher in non-drinkers. However, among regular drinkers there was a significant positive correlation between alcohol ingestion and femoral neck bone mineral density (Spearman's r = 0.53, p = 0.015). This study shows that the effect of nutrition seems dependent on the anatomical site assessed and that there is a weak correlation between nutritional intake and the actual bone mineral density.

Adult↗

An integrated YAC-overlap and 'cosmid-pocket' map of the human chromosome 21.

We describe here the construction of an ordered clone map of human chromosome 21, based on the identification of ordered sets of YAC clones covering > 90% of the chromosome, and their use to identify groups of cosmid clones (cosmid pockets) localised to subregions defined by the YAC clone map. This is to our knowledge the highest resolution map of one human chromosome to date, localising 530 YAC clones covering both arms of the chromosome, spanning > 36 Mbp, and localising more than 6300 cosmids to 145 intervals on both arms of the chromosome. The YAC contigs have been formed by hybridising a 6.1 equivalents chromosome 21 enriched YAC collection displayed on arrayed nylon membranes to a series of 115 DNA markers and Alu-PCR products from YACs. Forty eight mega-YACs from the previously published CEPH-Genethon map of sequence tagged sites (STS) have also been included in the contig building experiments. A YAC tiling path was then size-measured and confirmed by gel-fingerprinting. A minimal tiling path of 70 YACs were then used as probes against the 7.5 genome equivalents flow sorted chromosome 21 cosmid library in order to identify the lists of cosmids mapping to alternating shared--non-shared intervals between overlapping YACs ('cosmid pockets'). For approximately 1/5 of the minimal tiling path of YACs, locations and non-chimaerism have been confirmed by fluorescence in situ hybridisation (FISH), and approximately 1/5 of all cosmid pocket assignments have independent, confirmatory marker hybridizations in the ICRF cosmid reference library system. We also demonstrate that 'pockets' contain overlapping sets of cosmids (cosmid contigs). In addition to being an important logical intermediate step between the YAC maps published so far and a future map of completely ordered cosmids, this map provides immediately available low-complexity cosmid material for high resolution FISH mapping of chromosomal aberrations on interphase nuclei, and for rapid positional isolation of transcripts in the highly resolved regions of genetic interest.

Chromosome Mapping↗