Perinatal infections: HIV and co-infections in the placenta and therapeutic interventions-a workshop report.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
M Carneiro
Publications and source records attributed to M Carneiro.
Vertical HIV-1 transmission: prophylaxis and paediatric follow-up.
OBJECTIVES: To study the effectiveness of anti-HIV therapy for vertical HIV-1 transmission based on the PACTG protocol 076, modified and adapted to Venezuela. METHODS: Between March 1997 and March 2000, 74 HIV-1-infected women (15-42 years old) with 77 singleton pregnancies were evaluated. Zidovudine (ZDV) 500 mg/day (average 8 weeks) was begun after Western blot confirmatory tests, independent of CD4+ count or viral load. ZDV was administered as follows: 47 patients (61 per cent) received prenatal, perinatal and postnatal therapy; 13 (17 per cent) received prenatal and postnatal therapy; two (3 per cent) received prenatal and perinatal therapy; one patient received perinatal and postnatal therapy; seven (9 per cent) received only postnatal therapy. Seven HIV-1 infected women received no treatment. Thirty-two newborns were obtained by C-section (45.7 per cent), while 38 were delivered vaginally (54.2 per cent). Due to advanced maternal illness, seven HIV-1-infected women received ZDV+3TC, two women received ZDV+ddI and one woman received ZDV+3TC+ Ritonavir. Breastfeeding was avoided in all cases. RESULTS: Outcomes showed 65 term newborns and five preterm newborns; three abortions; one fetal loss and one preterm death. Two maternal/fetal deaths were secondary to complications related to AIDS at 27 and 29 weeks, respectively. Twenty-one children over 18 months old were considered uninfected. Thirty-five infants below 15 months of age were considered with the status of indeterminate HIV-1 infection (PO). Three infants fewer than 5 months of age with multiple risk factors were considered infected (P2). Two infants were asymptomatic and HIV positive at 12 months of age (P1). Eight children were lost to follow-up. CONCLUSIONS: Independent of maternal status and delivery type, confirmed vertical transmission of HIV-1-infected women who received ZDV is 4.25 per cent. Prenatal care with a multidisciplinary team is necessary for good obstetric and newborn outcomes.
Acquired Immunodeficiency Syndrome↗
[Assessment of the compliance to antiretroviral drugs among HIV/AIDS patients].
OBJECTIVES: To assess the compliance to antiretroviral drugs, and identify the main predictive factors and causes for treatment failure and poor compliance. METHODS: Twenty HIV/AIDS were randomly selected for the study. The assessment was carried out using self-reporting and complemented with diary and pharmacy checks. Univariate analysis was performed using Student test and Qui-square. Odds ratio was calculated as an inclusion measure. RESULTS: One hundred and twenty patients were assessed, of which 87 (72.5%) were males and 33 (27.5%) were females, with a mean age of 35.5 years old. Most of them were light dark skin, had completed only elementary school, and were employed, with an income of up to two minimum wages. The mean time of the antiretroviral use was 12 months. The main reason to initiate treatment was a decrease in CD4 lymphocyte counts to less than 350 cells/mm3. Most were taking three or more antiretrovirals. Eighty-nine patients (74%) were considered compliant. The main cause of treatment failure was the medication side effects. The educational level, age and time of antiretroviral use were the most important predictors of compliance to antiretrovirals. CONCLUSIONS: To improve treatment compliance there is a need to have treatment regimens with less side effects and treatment all the aspects should be constantly reviewed.
Acquired Immunodeficiency Syndrome↗
Nested case-control study in a serological survey to evaluate the effectiveness of a Chagas disease control programme in Brazil.
OBJECTIVE: To identify risk factors associated with Trypanosoma cruzi infections in areas under surveillance in the State of Minas Gerais, Brazil. METHODS: A model using a nested case-control design incorporated within a serological survey of schoolchildren which was employed to evaluate the effectiveness of the Chagas disease control programme. FINDINGS: In a sample of 40,374 schoolchildren (aged 7-14 years) surveyed, 16 children tested positive for T. cruzi antibody (by indirect immunofluorescence and indirect haemagglutination). In the case-control study, each case was randomly matched to three seronegative controls (classroom and age +/- 1 year). Compared to controls, T. cruzi-seropositive children were more likely to have a seropositive mother (odds ratio (OR) = 6.8; 95% confidence interval (CI) = 0.71-63.9) or a seropositive family member (OR = 8.6; 95% CI = 1.0-75.5). CONCLUSION: Use of the nested case-control model in a sero-epidemiological survey to evaluate risk factors for T. cruzi transmission was adequate for assessing the effectiveness of a Chagas disease control programme.
Adolescent↗
Design, implementation, and evaluation at entry of a prospective cohort study of homosexual and bisexual HIV-1-negative men in Belo Horizonte, Brazil: Project Horizonte.
BACKGROUND AND OBJECTIVES: Project Horizonte, an open cohort of homosexual and bisexual HIV-1-negative men, is a component of the Minas Gerais AIDS Vaccine Program of the Federal University of Minas Gerais, Belo Horizonte, Brazil. Its objectives included the evaluation of seroincidence of HIV, to ascertain the role of counseling on behavior modification and to assess their willingness to participate in future HIV vaccine trials. METHODS: Various means of recruitment were used, including pamphlets, notices in community newspapers, radio, and television, at anonymous testing centers, and by word of mouth. RESULTS: From October 1994 to May 1999, 470 volunteers were enrolled. Their mean age was 26 years and over 70% of them had high school or college education. During the follow-up, they were seen every 6 months, when they received counseling and condoms, and when HIV testing was done. Eighteen seroconversions were observed, and the incidence rates estimates were 1.75 per 100 and 1.99 per 100 person-years, for 36 and 48 months of follow-up, respectively. During the entire period, 139 volunteers were lost to follow-up. Among them, 59 (42.4%) never returned after the initial visit and 51 (36.7) came only once after their initial visit. No losses were observed for those observed during follow-up for more than 3 years. At enrollment, 50% of participants said they would participate in a vaccine trial, and 30% said they might participate. CONCLUSIONS: The results obtained up to this moment confirm the feasibility of following this type of cohort for an extended period, estimating HIV incidence rate, and evaluating counseling for safe sexual practices in preparation for clinical trials with candidate HIV vaccines in Brazil.
Adult↗
Role of the placenta in fetal HIV infection.
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Culture Techniques↗
A structural model for the rolA protein and its interaction with DNA.
The study of the plant oncogene rolA has been hampered by a lack of structural information. Here we show that, despite a lack of significant sequence similarity to proteins of known structure, the rolA sequence adopts a known fold; that of the papillomavirus E2 DNA-binding domain. This fold is reliably identified by modern threading programs, which consider predicted secondary structure, but not by others. Although the rolA sequence is only around 16% identical to those of the available template structures, a structural model could be built that performed well against protein structure verification programs. The adopted strategy involved alignment corrections, justified by multiple model building and evaluation, with particular attention paid to the hydrophobic core residues. We find that rolA protein is predicted to resemble the template proteins in two key aspects; existence as a dimer and ability to bind DNA. rolA protein has recently been shown experimentally to possess DNA binding ability. This model predicts Lys 24 and Arg 27 to be involved in sequence-specific interactions and eight other residues to hydrogen-bond phosphate groups of the DNA.
Amino Acid Sequence↗
HIV prevalence and risk behaviors among new initiates into injection drug use over the age of 40 years old.
Injection drug users (IDUs) who have recently initiated an injecting career have high risk behaviors for HIV infection. The average age of an IDUs first injection is typically reported as 19-20 years, and some literature has reported 'maturing out' of drug use typically around 40 years old. The purpose of this study was to discriminate risk behaviors among newer injectors by age of initiation. This cross-sectional study includes volunteers enrolled using extensive community recruitment techniques in 1988 and 1989 in Baltimore, MD. Of the 722 injection drug users who had initiated injection within the prior six years, 124 were over 35 years old of whom 53 were 40 years and older. Rates of HIV were lower among those over 40 years (13.2%) than those who were 35-39 years (22.5%) or under 35 years old (20.9%). The behavioral characteristics of those aged 35-39 were similar to those under 35 years old, but those over 40 years old when compared with less than 39 years reported injecting at least daily less frequently (88.7% vs 76.5%, p = 0.042), using a needle from a sterile wrapper (19.0% vs 36.6%, p = 0.006), and injecting with their own works (52.6% vs 28.8%, p = 0.021). This study shows that people initiate injection drug use across a wide age range and that needle hygiene practices early after initiation tend to be safer in older compared to younger initiates.
Adult↗
The effect of drug-injection behavior on genetic evolution of HIV-1.
The effect of injection-drug use on human immunodeficiency virus type 1 (HIV-1) env genetic evolution was examined in 15 seroconverting injection-drug users followed up for 4 years. After adjustment for non-drug-related independent variables significantly associated with genetic diversity (time since seroconversion and progressor status), injection frequency was positively and highly significantly associated with HIV-1 env genetic diversity (P=.003). The mutation rate in those who had injected at least once a day during the previous 6 months was estimated to be 62% greater than the rate in those who had not injected at all. If the positive effect of drug-injection frequency on env genetic diversity extends to the HIV-1 pol gene, the risk of emergence of resistance to antiretroviral drugs may be enhanced by increased drug-injection frequency, especially under the selection pressure of antiretroviral therapy.
Adult↗
Chagas Disease Control Programme in Brazil: a study of the effectiveness of 13 years of intervention.
Reported is an evaluation of 13 years of intervention by the Chagas Disease Control Programme in an endemic area (Montalvania) in the State of Minas Gerais, Brazil. The design used was an epidemiological panel study. The reduction of Trypanosoma cruzi infection rates was estimated from data collected on three separate occasions: a serological survey in 1975-80, a quasi-experimental study in 1987, and the present investigation. A random sample of 156 households was selected and blood samples were collected from 653 inhabitants. The data routinely collected by the control programme were analysed to correlate the results with the incidence of T. cruzi. The overall prevalence of infection was 2.3%; however, no participant under 14 years of age was found to have a positive serological test. The total reduction in T. cruzi infection rates in this area from the start of the programme's activities was estimated to be 83.5%. Cross-sectional comparisons for the age groups 2-6 years and 7-14 years indicated a 100% reduction in T. cruzi incidence rates; but cohort comparisons showed that 100% reduction was achieved only for the 2-6-years age group.
Adolescent↗
Tissue-specific expression of the rolA gene mediates morphological changes in transgenic tobacco.
The spatial and temporal activity of the entire and individual promoter domains of the rolA gene of Agrobacterium rhizogenes was investigated and correlated with the distinctive features of the phenotypes of transgenic tobacco plants. The GUS assay was performed in the presence of an oxidative catalyst during the development of transgenic plants expressing chimeric genes containing the beta-glucuronidase coding sequence under the control of the different promoter domains. In situ hybridization was also used on transgenic plants harbouring rolA under the control of the entire or deleted promoter. This paper demonstrates for the first time that the entire rolA promoter, composed of domains, A, B and C, is silent in seeds, then activated at the onset of germination in the cotyledons and in the elongation zone of the radicle and is finally expressed throughout the vegetative and floral phases. Domains B + C, which were sufficient to induce wrinkled leaves and short internodes, were active in all the stem tissues, but only in the companion cells of the phloem strands of the leaves. Domain C, which specified a dwarf phenotype with normal leaves, was weakly expressed in the stem vascular bundles and in the leaf internal phloem. These results indicate that the vascular bundles are the primary targets for the generation of the short internode phenotype. Furthermore, the local expression of rolA in the stem vascular bundles induced a size reduction of the surrounding parenchyma cells, suggesting the existence of some diffusible factor(s) associated with the expression of the rolA gene.
Bacterial Proteins↗
A quasi-experimental epidemiological model for evaluating public health programmes: efficacy of a Chagas disease control programme in Brazil.
Reported is the assessment of a model to evaluate the efficacy of public health programmes, using the example of the Chagas Disease Control Programme in the State of Minas Gerais, Brazil. The reduction in Trypanosoma cruzi infection rates in areas where interventions had been carried out for 5 years and 10 years, respectively, were compared with those where there had been no intervention (controls). A random sample of 470 households was selected and blood samples were collected from the 2354 inhabitants, 854 (36.3%) of whom were born after the start of the control programme. The data routinely collected by the control programme were also analysed to correlate the results with the incidence of T. cruzi infection. The programme efficacy was estimated by comparing the infection rates found in the study with those published by the Chagas Disease Serological Study (1975-80). Cross-sectional comparison of the data for the age group 2-6 years indicated that there had been a reduction in T. cruzi infection incidences of 94.7%, 63.2%, and 65%, respectively, in areas where interventions had been carried out for 10 years, 5 years, and in the control areas. Cohort comparison indicated, however, that the reduction (52.6%) occurred only in the intervention-10 area.
Adolescent↗
Differential expression of the rolA plant oncogene and its effect on tobacco development.
The rolA gene not only provokes the abnormal traits of wrinkled leaves, shortened internodes, and deficient root growth in tobacco, but also induction of roots in leaf disks in hormone-free medium. The rolA mRNA is most abundant in the stem of transgenic tobacco, accumulating at fivefold and 50-fold lower levels in the leaf and the root, respectively. Promoter deletion mutants were constructed and the rolA-induced abnormal traits were exploited to identify promoter regulatory regions. The removal of specific promoter domains provokes the appearance of new patterns of rolA transcripts in leaves, stems and roots. These new patterns are correlated with the disappearance of specific abnormal trait, thereby identifying three functional domains. Domain A includes a mosaic motif composed of a putative GT-2 binding site and DUE-NDE elements. This domain positively regulates rolA gene expression in the leaf and negatively regulates it in the stem and root. Domains B and C, which contain sequences homologous to the OCS enhancer and to ASF-1 binding sites, respectively, generally activate the rolA gene expression in all tissues. The possible function of these elements on the regulation of the rolA gene is discussed.
Base Sequence↗
[Echocardiographic evaluation of pulmonary valve stenosis for valvuloplasty in children and adults].
OBJECTIVES: 1--To determine the accuracy of the echocardiographic selection and characterization of the pulmonary stenosis (PS) for balloon valvuloplasty; 2--To analyze the differences between children and adults in obtaining the echocardiographic parameters used for pulmonary stenosis characterization. MATERIAL AND METHODS: We studied 53 consecutive patients with PS and a peak Doppler gradient > or = 40 mmHg, submitted to cardiac catheterization to perform balloon valvuloplasty if the right ventricle to pulmonary artery peak-to-peak systolic pressure gradient was > or = 40 mmHg. The patients were divided into 3 groups on the basis of age: < or = 5 years (group 1; n = 18), 6-16 years (group 2; n = 17) and > 16 years (group 3; n = 18). A complete echocardiographic study was performed including identification of valvular morphology (commissural fusion, dysplasia or mixed), determination of right ventricle to pulmonary artery peak Doppler gradient and the transducer position that yielded the highest transvalvular flow velocity (V), evaluation of the right ventricular outflow tract morphology and measurement of the valvular annulus diameter. RESULTS: Technically adequate recordings were obtained in all patients. Fifty patients (94%) were submitted to pulmonary valvuloplasty. The echo-Doppler recording of V was obtained from the parasternal position in 27 patients (51%), suprasternal in 14 (26%), subcostal in 10 (19%) and apical in 2. In group 1, the V was obtained from the suprasternal position in 8 patients (44%), subcostal in 5 (28%), parasternal in 4 (22%) and apical in 1. In group 2, it was the parasternal position in 8 patients (47%), suprasternal in 6 (35%), subcostal in 2 (12%) and apical in 1. In group 3, it was the parasternal position in 15 patients (83%) and subcostal in 3. The peak Doppler gradient ranged from 40 to 215 mmHg (mean +/- SD = 78 +/- 37) and the peak-to-peak gradient at cardiac catheterization from 32 to 220 mmHg (mean +/- SD = 81 +/- 41). The correlation between eco-Doppler peak gradient and peak-to-peak gradient at cardiac catheterization was r = 0.95 (SEE = 12 mmHg) being, for group 1, r = 0.89 (SEE = 14 mmHg), for group 2, r = 0.97 (SEE = 8 mmHg) and, for group 3, r = 0.98 (SEE = 10 mmHg). The right ventricular outflow tract shows dynamic reaction 48 patients. Two patients had an infundibular gradient > 25 mmHg, significantly underestimated by echo-Doppler in one. All 5 patients (9%) but one with angiographic criteria for valvular dysplasia, were identified by echocardiography. One patient had a mixed form. The remaining 47 patients had valvular commissural fusion. The annulus size measured by echocardiography ranged from 10 to 28 mm (mean +/- SD = 17.7 +/- 4.3) and by angiography from 10 to 28 mm (mean +/- SD = 17.6 +/- 4.4). Close correlations were found between echocardiographic and angiographic measurements: r = 0.97 (SEE = 1.1 mm) being, for group 1, r = 0.90 (SEE = 1.1 mm), for group 2, r = 0.94 (SEE = 0.8 mm) and, for group 3, r = 0.87 (SEE = 1.3 mm). CONCLUSION: The echocardiographic examination allows an accurate selection and characterization of the PS for balloon valvuloplasty. The most significant difference in the study of PS in children and adults, was the lack in the ability of the eco-Doppler to record the V from the suprasternal position in adults. 2D echocardiography can reliably measure the annulus diameter in children and adults, providing precise information for balloon diameter selection before valvuloplasty.
Adolescent↗
Spatial and temporal gene expression patterns occur during corm development.
We investigated gene expression patterns that occur during taro corm development. Two-dimensional gel electrophoresis identified several different prevalent proteins that accumulate during corm development. Microsequencing studies indicated that some of these proteins are related to taste-modifying proteins, such as curculin and miraculin, and proteins found in other storage organs, such as sporamin and the Kunitz trypsin inhibitor. A curculin-encoding cDNA clone, designated as TC1, was identified that corresponds to a highly prevalent 1-kb corm mRNA. The TC1 mRNA accumulates during corm development, is more prevalent in corm apical than basal regions, and is either absent, or present at low concentrations, in other vegetative organs such as the leaf and root. In situ hybridization experiments showed that the TC1 mRNA is highly concentrated in corm storage parenchyma cells and is absent, or present in reduced concentrations, in other corm cells and tissues. Our results show that corm development is associated with the differentiation of specialized cells and tissues, and that these differentiation events are coupled with the temporal and spatial expression of corm-specific genes.
Amino Acid Sequence↗
Isolation, characterization and expression of a gene coding for a 2S albumin from Bertholletia excelsa (Brazil nut).
Two genes, BE2S1 and BE2S2, coding for methionine-rich albumins of Brazil nut (Bertholletia excelsa H.B.K.) have been cloned and their sequence determined. The genes are members of a multigene family and one of them, i.e. BE2S1, codes for one of the dominant 2S isoforms. Its expression is highly regulated during seed development and with respect to tissue specificity. Sequence analysis has shown that the genes contain one intron and that the promoter of BE2S1 shows a canonical TATA motif. The transcription initiation site is located 26 nucleotides downstream from the TATA box. Sequence comparison of the promoter regions of 2S genes from Brassica napus, Arabidopsis thaliana and B. excelsa revealed the presence of TGCA palindromic sequence that appear to be arranged in a 2S-specific manner.
2S Albumins, Plant↗
Changes in the isoenzyme and kinetoplast DNA patterns of Trypanosoma cruzi strains induced by maintenance in mice.
Culture forms of thirteen Trypanosoma cruzi strains from 4 zymodemes and 9 schizodemes were inoculated and kept by successive passages in C3H mice. The strains were initially from the following zymodemes: 3 from A, 3 from B, 4 from C and 2 from D and 1 from AB mixed zymodemes. After approximately 18 months maintenance the parasites were isolated by hemoculture and again typed according to their isoenzyme and kinetoplast DNA patterns. The zymodeme A strains kept their initial patterns; from the 3 zymodeme B strains, two kept the initial patterns and one changed to zymodeme A; from the 4 zymodeme C, two kept the initial pattern and two changed to zymodeme B; from the 2 zymodeme D strains, one kept the initial pattern and one changed to zymodeme A. The strain from AB mixed zymodeme was reduced to zymodeme. A. The zymodeme changes were accompanied by schizodeme changes. Although not simultaneously, in one T. cruzi strain the parasitemia change was followed by zymodeme and schizodeme changes. The results showed that prolonged maintenance of T. cruzi in mice by successive passages alters the isoenzyme and k-DNA patterns of some strains and that these alterations tend to move towards zymodeme A, suggesting a selective effect of mice over these T. cruzi populations.
Animals↗
Tissue-specific in vitro transcription from the mouse albumin promoter.
Transcriptionally active nuclear extracts have been prepared from rat liver, brain, and spleen. The adenovirus-2 major late promoter directs efficient transcription by RNA polymerase II in all of these extracts, whereas the promoter of the mouse albumin gene is significantly used only in the liver extract. Albumin sequences located between -170 and -55 are required for this liver-specific in vitro transcription, since deletion of this region results in almost a 100-fold reduction in transcription. In addition, insertion of these sequences in either orientation upstream of the parotid-specific Amy-1 promoter, which is poorly transcribed in the liver extract, increases the activity of this promoter to a level comparable to that observed for the albumin promoter.
Adenoviridae↗