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Biomedical subjects

J Andrade

Publications and source records attributed to J Andrade.

At least 19 recordsLinked to original sources

Comparative genomic hybridization analysis identifies gains of 1p35 approximately p36 and chromosome 19 in osteosarcoma.

Osteosarcomas (OS) are aggressive tumors of the bone and often have a poor prognosis. Conventional cytogenetic analyses of OS have revealed highly complex karyotypes, with numerous abnormalities. In this study, we analyzed 18 untreated OS tumors from 17 patients of the younger incidence age group by comparative genomic hybridization (CGH), 4 tumors by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Comparative genomic hybridization identified frequent copy number changes of the chromosomal region 1p (10/17) and gain of part or all of chromosome 19(8/17). In addition gains were observed at 5p(3/17), 8q(3/17), 16p(3/17), and 17p(5/17); and losses at chromosomes 2q(3/17), 10(4/17) and 13(3/17). High level gains were detected in the 8q23 approximately q24 region in two tumors as well as at 17p in one primary and a metastatic tumor. Minimal regions of gain were present at 1p35 approximately p36.3 (8/17); 5p14 approximately p15.2 (3/17), and 8q22 approximately q24.3 (3/17). SKY analysis demonstrated that OS has a complex pattern of clonal and non-clonal rearrangements and helped confirm the structural basis for the imbalances detected by CGH. Spectral karyotyping confirmed an overall pattern of chromosomal gain affecting 1p in all four tumors. Fluorescence in situ hybridization analysis from these tumors confirmed the gain of the 1p36 region in 2 tumors as determined by CGH analysis as well as the amplification of 8q.

Bone Neoplasms↗

Comparing the effects of stimulation and propofol infusion rate on implicit and explicit memory formation.

Doubt remains about the conditions under which learning persists despite anaesthesia. This study investigated the relative importance of dose of anaesthetic and stimulation for learning during propofol infusion before surgery. Thirty-six patients were randomly assigned to three groups. Group 1 received two word lists (category examples and nonsense words) during infusion of propofol to a target concentration of 2 microg ml(-1). Groups 2 and 3 received the word lists during infusion of propofol 5 microg ml(-1). Group 2 received nonsense words before tracheal intubation and category examples during intubation; Group 3 heard category examples before and nonsense words during intubation. Bispectral index was recorded as a measure of depth of sedation/anaesthesia. We assessed explicit memory on recovery using a structured interview and a recognition test. We assessed implicit memory using a category generation test and a preference rating task. To establish baseline, a control group of 12 patients completed the category generation test without receiving the category examples during anaesthesia. Overall, there was no evidence for learning during propofol infusion, though the category generation task showed a trend towards more implicit memory for words presented during intubation than during anaesthesia. We conclude that learning does not occur during anaesthesia without surgery.

Anesthetics, Intravenous↗

Regulation of carbon and electron flow in Clostridium butyricum VPI 3266 grown on glucose-glycerol mixtures.

The metabolism of Clostridium butyricum was manipulated at pH 6.5 and in phosphate-limited chemostat culture by changing the overall degree of reduction of the substrate using mixtures of glucose and glycerol. Cultures grown on glucose alone produced only acids (acetate, butyrate, and lactate) and a high level of hydrogen. In contrast, when glycerol was metabolized, 1,3-propanediol became the major product, the specific rate of acid formation decreased, and a low level of hydrogen was observed. Glycerol consumption was associated with the induction of (i) a glycerol dehydrogenase and a dihydroxyacetone kinase feeding glycerol into the central metabolism and (ii) an oxygen-sensitive glycerol dehydratase and an NAD-dependent 1,3-propanediol dehydrogenase involved in propanediol formation. The redirection of the electron flow from hydrogen to NADH formation was associated with a sharp decrease in the in vitro hydrogenase activity and the acetyl coenzyme A (CoA)/free CoA ratio that allows the NADH-ferredoxin oxidoreductase bidirectional enzyme to operate so as to reduce NAD in this culture. The decrease in acetate and butyrate formation was not explained by changes in the concentration of phosphotransacylases and acetate and butyrate kinases but by changes in in vivo substrate concentrations, as reflected by the sharp decrease in the acetyl-CoA/free CoA and butyryl-CoA/free CoA ratios and the sharp increase in the ATP/ADP ratio in the culture grown with glucose and glycerol compared with that in the culture grown with glucose alone. As previously reported for Clostridium acetobutylicum (L. Girbal, I. Vasconcelos, and P. Soucaille, J. Bacteriol. 176:6146-6147, 1994), the transmembrane pH of C. butyricum is inverted (more acidic inside) when the in vivo activity of hydrogenase is decreased (cultures grown on glucose-glycerol mixture). For both cultures, the stoichiometry of the H(+) ATPase was shown to remain constant and equal to 3 protons exported per molecule of ATP consumed.

Carbon↗

Effects of visuospatial tasks on desensitization to emotive memories.

OBJECTIVES: Intrusive memories of extreme trauma can disrupt a stepwise approach to imaginal exposure. Concurrent tasks that load the visuospatial sketchpad (VSSP) of working memory reduce the vividness of recalled images. This study tested whether relief of distress from competing VSSP tasks during imaginal exposure is at the cost of impaired desensitization. DESIGN: This study examined repeated exposure to emotive memories using 18 unselected undergraduates and a within-subjects design with three exposure conditions (Eye Movement, Visual Noise, Exposure Alone) in random, counter-balanced order. METHOD: At baseline, participants recalled positive and negative experiences, and rated the vividness and emotiveness of each image. A different positive and negative recollection was then used for each condition. Vividness and emotiveness were rated after each of eight exposure trials. At a post-exposure session 1 week later, participants rated each image without any concurrent task. RESULTS: Consistent with previous research, vividness and distress during imaging were lower during Eye Movements than in Exposure Alone, with passive visual interference giving intermediate results. A reduction in emotional responses from Baseline to Post was of similar size for the three conditions. CONCLUSION: Visuospatial tasks may offer a temporary response aid for imaginal exposure without affecting desensitization.

Adolescent↗

Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study.

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: </=90 (n=6264); </=85 (n=6264); </=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure</=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure </=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of </=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of </=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels </=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure </=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.

Aged↗

Stenting as first option for endovascular treatment of malignant superior vena cava syndrome.

OBJECTIVE: Endoprostheses were inserted in cancer patients with superior vena cava syndrome to assess their effectiveness as first-choice, initial treatment for relief of symptoms. SUBJECTS AND METHODS: Wallstent prostheses (n = 73) of various lengths (5-14 cm; median, 7 cm) and diameters (10-16 mm; median, 16 mm) were inserted in 52 cancer patients (51 men, 1 woman; age range, 44-78 years; mean, 63 years) who were diagnosed and confirmed by cavography or phlebography as having superior vena cava syndrome. A single stent was sufficient in 37 patients, two stents were required in 11, three stents in two, and four stents in another two patients. Contraindications for the procedure were severe cardiopathy or coagulopathy. RESULTS: Resolution of symptoms was achieved in all patients within 72 hr. At follow-up, six obstructions, one partial migration to the right atrium, two incorrect placements, and four stent "shortenings" were noted. All were successfully resolved by repeated stenting. Symptom-free survival ranged from 2 days to 17 months (mean, 6.4 months). At the time of this writing, eight patients are alive and have patent stents. The rest have died from their cancer. CONCLUSION: The Wallstent vascular endoprosthesis is an effective initial treatment in superior vena cava syndrome of neoplastic origin. Morbidity and complications are minimal. Clinical relief of symptoms is rapid; therefore, the Wallstent endoprosthesis is highly recommended as the first choice for palliative treatment of superior vena cava syndrome, especially because the clinical decision for subsequent chemotherapy or radiotherapy or surgery is not in any way prejudiced.

Adult↗

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↗

The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton.

Arf family GTP-binding proteins are best characterized as regulators of membrane traffic, but recent studies indicate an additional role in cytoskeletal organization. An Arf GTPase-activating protein of the centaurin beta family, ASAP1 (also known as centaurin beta4), binds Arf and two other known regulators of the actin cytoskeleton, the tyrosine kinase Src and phosphatidylinositol 4,5-bisphosphate. In this paper, we show that ASAP1 localizes to focal adhesions and cycles with focal adhesion proteins when cells are stimulated to move. Overexpression of ASAP1 altered the morphology of focal adhesions and blocked both cell spreading and formation of dorsal ruffles induced by platelet-derived growth factor (PDGF). On the other hand, ASAP1, with a mutation that disrupted GTPase-activating protein activity, had a reduced effect on cell spreading and increased the number of cells forming dorsal ruffles in response to PDGF. These data support a role for an Arf GTPase-activating protein, ASAP1, as a regulator of cytoskeletal remodeling and raise the possibility that the Arf pathway is a target for PDGF signaling.

3T3 Cells↗

Working memory and the vividness of imagery.

The working memory framework was used to investigate the factors determining the phenomenological vividness of images. Participants rated the vividness of visual or auditory images under control conditions or while performing tasks that differentially disrupted the visuospatial sketchpad and phonological loop subsystems of working memory. In Experiments 1, 2, and 6, participants imaged recently presented novel visual patterns and sequences of tones; ratings of vividness showed the predicted interaction between stimulus modality and concurrent task. The images in experiments 3, 4, 5, and 6 were based on long-term memory (LTM). They also showed an image modality by task interaction, with a clear effect of LTM variables (meaningfulness, activity, bizarreness, and stimulus familiarity), implicating both working memory and LTM in the experience of vividness.

Adolescent↗

Phonological similarity and the irrelevant speech effect: implications for models of short-term verbal memory.

Three experiments studied the interaction between irrelevant speech and phonological similarity within both the remembered and the irrelevant auditory material. Phonological similarity within the remembered list impaired performance in both baseline and irrelevant speech conditions, whereas phonological similarity between the remembered and ignored irrelevant items did not influence performance. Although there was a tendency for similarity within the irrelevant items to reduce interference, this proved to be a less robust finding. Implications for the theoretical interpretation of the irrelevant speech effect are discussed.

Female↗

An investigation of learning during propofol sedation and anesthesia using the process dissociation procedure.

BACKGROUND: Many studies have shown that patients may remember words learned during apparently adequate anesthesia. Performance on memory tests may be influenced by explicit and implicit memory. We used the process dissociation procedure to estimate implicit and explicit memory for words presented during sedation or anesthesia. METHODS: We investigated intraoperative learning in 72 women undergoing pervaginal oocyte collection during propofol and alfentanil infusion. One word list was played once before infusion, another was played 10 times during surgery. Venous blood was taken for propofol assay at the end of the intraoperative list. Behavioral measures of anesthetic depth (eyelash reflex, hand squeeze response to command) were recorded and used to adjust the dose of anesthetic where clinically appropriate. On recovery, memory was assessed using an auditory word stem completion test with inclusion and exclusion instructions. RESULTS: The mean blood propofol concentration was 2.5 microg/ml (median, 2.3 microg/ml; range, 0.7-6.1 microg/ml). Mean alfentanil dose was 2.1 mg (median, 2.0 mg; range, 1.2-3.4 mg). Comparison of target and distractor hits in the inclusion condition showed memory for preoperative words only. However, the process dissociation procedure estimates showed explicit (mean, 0.18; P < 0.001) and implicit (mean, 0.05; P < 0.05) memory for the preoperative words, and a small amount of explicit memory for the intraoperative words (mean, 0.06; 95% confidence interval, 0.01-0.10). Memory performance did not differ between the 17 patients who consistently responded to command and eyelash reflex and the 32 patients who remained unresponsive. Blood propofol concentration and alfentanil dose did not correlate with memory for the intraoperative list. CONCLUSIONS: There was no unprompted recall of surgery, but the process dissociation procedure showed memory for words presented during surgery. This memory was apparently explicit but did not correlate with the measures of depth of anesthesia used.

Adult↗

Long-term effects of a nationwide control program on the seropositivity for Trypanosoma cruzi infection in young men from Argentina.

Unselected nationwide cohorts of Argentine men 18 years of age summoned for military service were tested for antibodies to Trypanosoma cruzi each year from 1981 to 1993. After an initial screening using indirect hemagglutination test, the positive sera were retested by titrated indirect hemagglutination and immunofluorescence antibody tests at 39 laboratories or at the national reference center in Buenos Aires. Nearly 1.8 million men were examined for T. cruzi antibodies using the same standardized procedures under a quality assurance program. The prevalence of seropositivity for T. cruzi decreased significantly from 5.8% in 1981 to 1.9% in 1993, but the decrease was not homogeneous among provinces within each region or constant over time. Prior to the nationwide control campaign initiated in 1961-1962, 15 provinces had high (> 20%) percentages of houses with domiciliary infestation by Triatoma infestans bugs, which decreased to nine provinces in 1982, and four provinces in 1992. The observed decrease in the prevalence of seropositivity for T. cruzi may be mostly attributed to the spraying with insecticides to eliminate the domiciliary populations of Triatoma infestans. The lack of a sustainable triatomine surveillance program set a limit to the decrease of seropositivity rates and prompted a revised strategy based on community participation.

Adolescent↗

Homogeneous bioluminescence assay for galactosuria: interference and kinetic analysis.

Elevated galactose concentration in urine is an important clinical symptom of galactosemia and other metabolic disorders. A quantitative assay for galactose using firefly luciferase bioluminescence is presented. The assay couples the galactokinase and firefly luciferase reactions. A higher concentration of galactose present in the sample produces a faster decrease in ATP concentration, which is monitored by firefly luciferase bioluminescence. The kinetic assay is modeled and analyzed. The interference between the two reactions, the interference of certain sugars and other components in the urine, the specificity, and the optimal pH for galactokinase were studied. Calibration curves were constructed and compared with a conventional spectrophotometric assay for galactose. The bioluminescence assay is relatively fast and specific for galactose with a linear range from 1 to 20 mM galactose. The effect of other galactose metabolites (galactonate and galactitol) has also been studied.

Adenosine Triphosphate↗

Morphological characterization of lung and kidney lesions in C3H/HeJ mice infected with Leptospira interrogans serovar icterohaemorrhagiae: defect of CD4+ and CD8+ T-cells are prognosticators of the disease progression.

Neonates and young C3H/HeJ mice were highly susceptible to lethal infection with Leptospira interrogans serovar icterohaemorrhagiae. The main pathological changes were seen by light microscopy in the lung and kidneys of 3-week-old mice at 11 days after inoculation. Lung histological lesions included small and medium-sized vasculitis with fibrinoid changes, hemorrhages, moderate infiltrate of mononuclear inflammatory cells and fibrin thrombi. In the kidney there was mild to severe acute tubular necrosis associated with interstitial nephritis. Repair of damaged tubules in surviving mice was observed within 17 days after inoculation. Pathological findings of CD4+ and CD8+ cell-depleted mice were clearly more severe than that seen in untreated animals by 17 days after inoculation. Comparatively, CD4+/CD8+ cell-depleted mice had more marked lung and kidney lesions than in the CD8+ or CD4+ cell-depleted mice. A very high level of tubular alterations was seen in the kidneys of all treated groups. Increased degrees of interstitial nephritis also reflected the T-cell subsets depletion related events. Leptospires were clearly demonstrated by immunoperoxidase close to the sites of histological damage in all infected mice. C3H/HeJ mice represent a useful model for further studies in pathogenicity of leptospires and natural resistance of the host.

Animals↗

ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src.

Membrane trafficking is regulated in part by small GTP-binding proteins of the ADP-ribosylation factor (Arf) family. Arf function depends on the controlled exchange and hydrolysis of GTP. We have purified and cloned two variants of a 130-kDa phosphatidylinositol 4, 5-biphosphate (PIP2)-dependent Arf1 GTPase-activating protein (GAP), which we call ASAP1a and ASAP1b. Both contain a pleckstrin homology (PH) domain, a zinc finger similar to that found in another Arf GAP, three ankyrin (ANK) repeats, a proline-rich region with alternative splicing and SH3 binding motifs, eight repeats of the sequence E/DLPPKP, and an SH3 domain. Together, the PH, zinc finger, and ANK repeat regions possess PIP2-dependent GAP activity on Arf1 and Arf5, less activity on Arf6, and no detectable activity on Arl2 in vitro. The cDNA for ASAP1 was independently identified in a screen for proteins that interact with the SH3 domain of the tyrosine kinase Src. ASAP1 associates in vitro with the SH3 domains of Src family members and with the Crk adapter protein. ASAP1 coprecipitates with Src from cell lysates and is phosphorylated on tyrosine residues in cells expressing activated Src. Both coimmunoprecipitation and tyrosine phosphorylation depend on the same proline-rich class II Src SH3 binding site required for in vitro association. By directly interacting with both Arfs and tyrosine kinases involved in regulating cell growth and cytoskeletal organization, ASAP1 could coordinate membrane remodeling events with these processes.

ADP-Ribosylation Factor 1↗

[The Sézary syndrome].

Sézary syndrome is a form of cutaneous T-cell lymphoma and, like mycosis fungoides, results from the malignant proliferation of mature post-thymic T-cell lymphocytes. The main features are the presence of abnormal mononuclear cells (Sezary cells) in the peripheral blood and exfoliative erythroderma. The authors present of a 70-year-old woman admitted to our clinic due to the case pruriginous and exfoliative erythroderma, subcutaneous nodes and lymphadenopathy. The clinical diagnosis of Sézary syndrome was confirmed through the identification of Sézary cells in the peripheral blood by cytochemistry and membrane marker studies and by lymph node histopathology. Genotypic studies excluded the presence of HTLV-I and HTLV-II sequences in DNA samples and confirmed the monoclonal nature and T-cell origin of this lymphoproliferative disease.

Aged↗

Mutation analysis of the BRCA2 gene in breast/ovarian cancer Spanish families: identification of two new mutations.

The recently isolated gene BRCA2 is responsible for about 45% of familial breast cancer and the majority of male breast cancer families. We have screened 12 high risk breast/ovarian Spanish families for mutations in BRCA2, using SSCP followed by direct sequencing. We have found mutations in four of our 12 families (33.3%), including two with male breast cancer. Three of the mutations were frameshift and one was a missense. Two of the mutations have been previously published and two are new mutations.

Adult↗