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Biomedical subjects

M Barbosa

Publications and source records attributed to M Barbosa.

18 recordsLinked to original sources

Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation.

The present study examines the effects of forskolin on U937 cell differentiation. We recently reported that dibutyryl cAMP (dbcAMP), but not cAMP-elevating agents such as histamine, promotes U937 cell differentiation. cAMP production elicited by stimulation of histamine H2 receptors showed a rapid, homologous desensitization, which might explain the dissimilar responses to histamine and dbcAMP. Forskolin induced an increase in cAMP levels in a concentration-dependent manner (EC50=30 microM) for an extended period of at least 24 h. Forskolin but not histamine (up to 100 microM), also inhibited cell growth in a dose-dependent fashion (EC50=22 microM). After 3 days of incubation, 75 microM forskolin induced U937 cell differentiation as judged by an increased rate of reduction of nitrobluetetrazolium (mean+/-S.E.M.: 21.3+/-6.6% in treated cells vs. 3.2+/-1.9% in the control group, P < 0.001) and an augmented chemotactic response to complement 5a (C5a) (33.2+/-5.9% in forskolin-treated vs. 0.34+/-0.12% in control cells, P < 0.01). Furthermore, c-Myc levels decreased following forskolin treatment, while the histamine H2 receptor agonist dimaprit had no effect. We conclude that forskolin induces U937 cell differentiation through a sustained rise in cAMP levels.

Antigens, Neoplasm

HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF-kappaB activation.

NF-kappaB, a key regulator of the cellular inflammatory and immune response, is activated by the HTLV-I transforming and transactivating protein Tax. We show that Tax binds to the amino terminus of the protein kinase MEKK1, a component of an IkappaB kinase complex, and stimulates MEKK1 kinase activity. Tax expression increases the activity of IkappaB kinase beta (IKKbeta) to enhance phosphorylation of serine residues in IkappaB alpha that lead to its degradation. Dominant negative mutants of both IKKbeta and MEKK1 prevent Tax activation of the NF-kappaB pathway. Furthermore, recombinant MEKK1 stimulates IKKbeta phosphorylation of IkappaB alpha. Thus, Tax-mediated increases in NF-kappaB nuclear translocation result from direct interactions of Tax and MEKK1 leading to enhanced IKKbeta phosphorylation of IkappaB alpha.

Animals

Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor suppressor gene.

Recent studies show that 1) the p53 tumor suppressor protein is overexpressed by rheumatoid arthritis (RA) synovium and fibroblast-like synoviocytes (FLS) and 2) somatic mutations previously identified in human tumors are present in RA synovium and FLS. We have hypothesized that abnormalities in p53 can contribute to chronic destructive RA synovitis. To understand the functional consequences of p53 abnormalities in FLS, RA and normal FLS expressing wild-type p53 were transduced with a retroviral vector encoding the human papilloma virus 18 E6 gene, which inactivates endogenous p53 protein. Three RA and one normal FLS lines were infected with recombinant retrovirus encoding the neomycin resistance gene (neo) or E6+neo. FLS proliferation, apoptosis, and invasion was studied in E6, neo, and uninfected parental strains (PS). The growth rate for E6 was significantly increased with a sixfold increase in cell number after 7 days compared with a twofold to threefold increase in neo and PS. When FLS were treated with cytokines, proliferative response of E6, neo, and PS to interleukin-1 and transforming growth factor-beta were similar. However, response to platelet-derived growth factor was significantly greater in E6 FLS compared with neo or PS. Apoptosis was studied by incubating FLS with sodium nitroprusside as a source of nitric oxide or hydrogen peroxide for 8 hours and examining DNA fragmentation and E6 cells were significantly less susceptible to cell death. In addition, E6 FLS were more invasive into cartilage extracts than neo or PS using an in vitro cell invasion assay. These data suggest that p53 is a critical regulator of FLS proliferation, apoptosis, and invasiveness. Abnormalities of p53 function might contribute to synovial lining expansion and joint destruction in RA.

Apoptosis

IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation.

Activation of the transcription factor nuclear factor kappa B (NF-kappaB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IkappaB. A large multiprotein complex, the IkappaB kinase (IKK) signalsome, was purified from HeLa cells and found to contain a cytokine-inducible IkappaB kinase activity that phosphorylates IkappaB-alpha and IkappaB-beta. Two components of the IKK signalsome, IKK-1 and IKK-2, were identified as closely related protein serine kinases containing leucine zipper and helix-loop-helix protein interaction motifs. Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway.

Cell Cycle Proteins

[Opinion of alumni about the teaching of nursing diagnosis according to North American Nursing Diagnosis Association].

In accordance to North American Nursing Diagnosis Association (NANDA), nursing diagnosis is a clinical judgement of the individual, family or community answers to the vital process or to the actual or potential health problems. These gives the basis for the intervention selection by which the nurse is responsible. Believing in the importance of nursing diagnosis, its teaching was introduced 4 years ago in the subjects of Woman s Health Assistance and Perinatal Nursing, in the 6o. period of the undergraduate course in nursing at UNICAMP. Aiming at evaluating these experience, we proposed to get the students opinion and obtain subsides to perfect teaching. Teoric teaching of 4 hours was given and it was indicated the basic bibliography. The supervised practical application was developed during 21 hours in a neonatal unit and 45 hours in health centers. At the end of the subjects, 16 students answered a form with closed and open questions. All the students considered valid the study of the nursing diagnoses. Most of the students considered more proper to introduce the teaching in the 3o. semester, when the nursing basic procedures is begun. As to the difficult of learning in the use of diagnoses, 68.7% of the students reported a difficult level higher to 25% and lower to 75%. The students group considers that the study of nursing diagnoses brought modifications in its concept of nursing assistance.

Attitude of Health Personnel

[Educational program in universal precaution measures: a methodological approach].

An updating program on measures of universal precautions (M.U.P.) was developed at the Center of Whole Care of Woman's Health (Centro de Atenção Integral à Saúde da Mulher-CAISM). These measures and the procedures in the case of work accident were published in a booklet. First, servants should be aware of the matter of stress and its influence on the quality of life. Then, updating was carried through encouraging the reflection on the consequences of the non-adoption of M.U.P. The answers to 286 pre-tests and 242 post-tests were analyzed and the results showed a significantly higher index of correct answers (p < 0.01), mainly regarding the appropriate use of glove.

Education, Nursing

[Incessant atrial tachycardia and peripartum cardiomyopathy--a therapeutic challenge].

Peripartum cardiomyopathy is an uncommon cause of heart failure but with serious prognosis. We report the case of a patient with peripartum cardiomyopathy presenting acute heart failure (severe biventricular systolic failure) and incessant atrial tachycardia, a rare arrhythmia difficult to control, that was responsible for cardiogenic shock, fetus death and multiple organ failure: renal failure (hemodialysis during 17 days), respiratory and hepatic failure and ischemic acute cholecystitis (treated surgically). After emergency cesarean section, heart rate control was obtained only after administering verapamil. Progressive clinical improvement with total recovery of hepatic and renal functions followed under treatment with vigorous multiple organ support. Six months after referral, the patients is doing well with normal daily life controlled with conventional therapy for heart failure, in stable sinus rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction. The use of verapamil in severe biventricular systolic failure is discussed.

Cardiomyopathies

Surgical repair of transposition of great arteries and total anomalous pulmonary venous return to the coronary sinus (TGA with TAPVR).

The association of transposition of the great arteries (TGA) and total anomalous pulmonary venous return (TAPVR) is very rare; we report one case of this malformation with an intracardiac type of TAPVR draining into the coronary sinus. The surgical repair was performed directing the coronary sinus blood flow to the tricuspid valve. The proximity of the anatomical structures allowed an intra-atrial patch repair similar to a modified Mustard procedure. In the postoperative period the child developed low cardiac output for 2 days, requiring inotropic support and mechanical ventilation. Her recovery was otherwise uneventful. The postoperative echocardiogram showed an intact repair with perfect flow through the patch from the pulmonary veins to the right ventricle. Almost 2 years after surgery, the patient underwent cardiac catheterization that showed integrity of the surgical repair with normal pressures in all heart chambers. To our knowledge this is the first report in the medical literature of surgical treatment of this association.

Coronary Circulation

Severe haemolytic disease in an infant born to an Rh(null) proposita.

A 35-year-old Brazilian woman (gravida 4, para 2) was delivered of a severely anaemic child whose cord red blood cells had a strongly positive direct antiglobulin test and who required two exchange transfusions within 24 h of birth. Because of the emergency of the situation and the lack of a local immunohaematology reference laboratory, the phenotype of the mother and the specificity of the relevant antibody could not be determined. Hence, compatible blood was not immediately available and the infant had to be given repeated exchange transfusions with incompatible group 0 Rh-negative blood. The infant is now healthy and thriving. The mother's red cells were subsequently found to lack all the antigens of the Rh system, and her serum reacted with all red cell samples except those of two unrelated Rh(null) individuals. Her serum gave high titres (i.e. 1,024-4,096) by the indirect antiglobulin test against red cells of normal Rh phenotype, as well as against cells with partially deleted Rh phenotypes (titres = 128-512 with -D-/-D- and .D./.D. samples, respectively), and was extremely active in antibody-dependent cell-mediated cytotoxicity and monocyte monolayer assays against red cells of normal Rh phenotypes.

Adult

[Use of coronary angioplasty in acute myocardial infarction without previous use of thrombolytic agents. Analysis of 201 patients].

PURPOSE: To evaluate the experience with the use of primary PTCA in the set of acute myocardial infarction (AMI) without the previous administration of thrombolytic agents. PATIENTS AND METHODS: Two hundred and one patients with AMI, aged 35 to 86 years (mean = 57.2). There were 83.5% men. Twenty patients were older than 70 years and 48.2% had an anterior AMI. PTCA was performed early in the AMI, with a delay no longer than 12 hours. In 95%, it was done solely to the infarct related artery. Seventy percent patients were in Killip class I, 21% in class II, and 8% in classes III and IV (more than 50% of this subset of patients were in cardiogenic shock). RESULTS: Primary success was achieved in 84.5%. In hospital mortality was 5.9%, and there were 7% reinfarctions. Among the 84 patients who underwent a late cinecoronariography study, there were 19% restenosis and 8.3% reocclusions. In the long term follow up 75% were asymptomatic. Repeat PTCA was required in 10.2% of the cases, late coronary surgery was performed on 10.8% of the patients, and post-hospital cardiac mortality was 8.8% during an average follow up of 28 months (range 2-72 months). CONCLUSION: Primary PTCA is a effective way of reperfusion in the AMI, with a high primary success, low complications rate and without any major contraindications.

Adult

Breast-feeding and fertility in Macau.

That fact that only a small percentage of women in Macau breast-feed induced the need to investigate this attitude. In collaboration with the Maternal & Child Health Division of the W.H.O., Geneva, it was decided that a methodology which had already been applied in other places should be used to investigate the relation between breast-feeding and fertility. In this way, information was obtained about the situation, within a given period of time which permitted a description of the duration of amenorrhea due to breast-feeding, as well as the patterns of frequency and duration of breast-feeding.

Adolescent

Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma.

Keratinocytes electroporated with human papillomavirus (HPV) DNA (HPV-6, 11, 16 and 18) exhibited an increased cellular proliferation which was quantitated as microcolony and macrocolony formation. However, only macrocolonies induced by HPV-16 or HPV-18 DNA (the two viral types most commonly found in human cervical carcinomas) gave rise to proliferating, poorly-stratified colonies when grown in the presence of serum and calcium. Hydrocortisone increased the frequency of these differentiation-resistant colonies, and studies showed that they were immortalized, contained one copy of viral DNA per cell, expressed three discrete species of viral RNA and synthesized the viral E7 protein. HPV-induced cellular proliferation and altered differentiation are therefore separable events and may represent the activity of different viral genes.

Biological Assay