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Biomedical subjects

V Oliveira

Publications and source records attributed to V Oliveira.

At least 19 recordsLinked to original sources

Translocation (8;17;15;21)(q22;q23;q15;q22) in acute myeloid leukemia (M2). a four-way variant of t(8;21).

We report the results of cytogenetic, fluorescence in situ hybridization (FISH) and molecular analyses in a 15-year-old boy diagnosed with acute myeloid leukemia subtype M2 (AML-M2). Cytogenetic and FISH analyses, the latter with whole chromosome painting probes, revealed a complex translocation involving four chromosomes: t(8;17;15;21)(q22;q23;q15;q22). The observation of breakpoints at 8q22 and 21q22 suggested a rearrangement of the ETO and AML1 genes, respectively. Using a dual-color FISH test with ETO and AML1 probes, we demonstrated an AML1/ETO fusion signal on the derivative chromosome 8. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed the presence of AML1/ETO fusion transcripts identical to those found in classical t(8;21). The present case highlights the relevant role of the rearranged chromosome 8, which encodes the AML1/ETO fusion product in the pathogenesis of AML-M2.

Adolescent↗

Selective neurotensin-derived internally quenched fluorogenic substrates for neurolysin (EC 3.4.24.16): comparison with thimet oligopeptidase (EC 3.4.24.15) and neprilysin (EC 3.4.24.11).

Internally quenched fluorescent peptides derived from neurotensin (pELYENKPRRPYIL) sequence were synthesized and assayed as substrates for neurolysin (EC 3.4.24.16), thimet oligopeptidase (EC 3.4.24.15 or TOP), and neprilysin (EC 3.4.24.11 or NEP). Abz-LYENKPRRPYILQ-EDDnp (where EDDnp is N-(2,4-dinitrophenyl)ethylenediamine and Abz is ortho-aminobenzoic acid) was derived from neurotensin by the introduction of Q-EDDnp at the C-terminal end of peptide and by the substitution of the pyroglutamic (pE) residue at N-terminus for Abz and a series of shorter peptides was obtained by deletion of amino acids residues from C-terminal, N-terminal, or both sides. Neurolysin and TOP hydrolyzed the substrates at P--Y or Y--I or R--R bonds depending on the sequence and size of the peptides, while NEP cleaved P-Y or Y-I bonds according to its S'(1) specificity. One of these substrates, Abz-NKPRRPQ-EDDnp was a specific and sensitive substrate for neurolysin (k(cat) = 7.0 s(-1), K(m) = 1.19 microM and k(cat)/K(m) = 5882 mM(-1). s(-1)), while it was completely resistant to NEP and poorly hydrolyzed by TOP and also by prolyl oligopeptidase (EC 3.4.21.26). Neurolysin concentrations as low as 1 pM were detected using this substrate under our conditions and its analogue Abz-NKPRAPQ-EDDnp was hydrolyzed by neurolysin with k(cat) = 14.03 s(-1), K(m) = 0.82 microM, and k(cat)/K(m) = 17,110 mM(-1). s(-1), being the best substrate so far described for this peptidase.

Alanine↗

Substrate specificity characterization of recombinant metallo oligo-peptidases thimet oligopeptidase and neurolysin.

We report a systematic and detailed analysis of recombinant neurolysin (EC 3.4.24.16) specificity in parallel with thimet oligopeptidase (TOP, EC 3.4.24.15) using Bk sequence and its C- and N-terminal extensions as in human kininogen as motif for synthesis of internally quenched fluorescent substrates. The influence of the substrate size was investigated, and the longest peptide susceptible to TOP and neurolysin contains 17 amino acids. The specificities of both oligopeptidases to substrate sites P(4) to P(3)' were also characterized in great detail using seven series of peptides based on Abz-GFSPFRQ-EDDnp taken as reference substrate. Most of the peptides were hydrolyzed at the bond corresponding to P(4)-F(5) in the reference substrate and some of them were hydrolyzed at this bond or at F(2)-S(3) bond. No restricted specificity was found for P(1)' as found in thermolysin as well for P(1) substrate position, however the modifications at this position (P(1)) showed to have large influence on the catalytic constant and the best substrates for TOP contained at P(1), Phe, Ala, or Arg and for neurolysin Asn or Arg. Some amino acid residues have large influence on the K(m) constants independently of its position. On the basis of these results, we are hypothesizing that some amino acids of the substrates can bind to different sub-sites of the enzyme fitting P-F or F-S bond, which requires rapid interchange for the different forms of interaction and convenient conformations of the substrate in order to expose and fit the cleavage bonds in correct position for an efficient hydrolysis. Finally, this plasticity of interaction with the substrates can be an essential property for a class of cytosolic oligopeptidases that are candidates to participate in the selection of the peptides to be presented by the MHC class I.

Amino Acid Sequence↗

HITS in internal carotid dissections.

Carotid dissections can cause neurological deficits either by hemodynamic or embolic mechanisms. Anticoagulants are often used in this setting to prevent neurological deterioration and stroke recurrence. High-intensity transient signals (HITS) detected by transcranial Doppler may be due to microembolism. We investigated the presence and number of HITS in a series of 27 patients with carotid dissection. HITS were detected in 14 (52%) patients and only in cases with a less than 7-day evolution. No association was found between HITS and clinical or imagiological features of the dissection nor with neurological aggravation or treatment type. We failed to demonstrate any relevant clinical significance of HITS in carotid dissection.

Adult↗

Hydrolysis by cathepsin B of fluorescent peptides derived from human prorenin.

Cathepsin B is a lysosomal thiolprotease that, because of its colocalization with renin and its ability to activate prorenin, has been proposed as a prorenin processing enzyme. To characterize the biochemical aspect of this potential cathepsin B activity in more detail, we synthesized and assayed with human cathepsin B the internally quenched fluorescent peptide Abz-FSQPMKRLTLGNTTQ-EDDnp (Abz, ortho-aminobenzoic acid fluorescent group and EDDnp, N-¿2, 4-dinitrophenyl-ethylenediamine quencher group) that contains 7 amino acids for each side of the R-L bond that is the processing site of human prorenin. Human cathepsin B hydrolyzed this peptide at the correct site (R-L bond), with k(cat)/K(m)=75 mmol/L(-1) s(-1). Analogues of this peptide obtained by Ala scanning at positions P(5) to P(5)' were also synthesized and assayed as substrates for human cathepsin B. The obtained specificity constant (k(cat)/K(m)) values have a significant parallel with the previous data of prorenin activation by AtT-20 cells and in vitro by cathepsin B. In addition, we demonstrated the presence of cathepsin B-like activity in rat mesangial cells and the ability of its whole soluble fraction lysates, as well as that of purified cloned rat cathepsin B, to hydrolyze Abz-IKKSSF-EDDnp at the K-S bond, which contains 6 amino acids of rat prorenin processing site. The specificity data of cathepsin B toward peptides derived from prorenin processing site support the view that human or rodent cathepsin B could be involved in the intracellular processing of prorenin that is locally synthesized or taken up from the extracellular compartment.

Animals↗

Characterization of thiol-, aspartyl-, and thiol-metallo-peptidase activities in Madin-Darby canine kidney cells.

We combined fluorogenic substrates or internally quenched fluorescent peptides with specific inhibitors in the pH profile of proteolytic activity experiments in order to detect proteolytic activities in lysates of MDCK cells. Hydrolytic activities related to cathepsin B, L, and D were observed. Serine-proteinase was not detected; however, we clearly demonstrated the presence of a thiol-metallo-endo-oligopeptidase, also called thimet-oligopeptidase (TOP). This peptidase from MDCK cells has substrate and inhibitor specificities as well as an activation profile with mercaptoethanol that are indistinguishable from the recombinant rat testis TOP (EC 3. 4.24.15). In addition, polyclonal purified antibodies to this enzyme depleted the TOP activity of MDCK cells in whole homogenate. Although we present only preliminary data, TOP is secreted by MDCK cells. The presence of TOP in a phenotype polarized MDCK cells can have special significance in the cytoplasmic selection, transport, or clearance of short peptides due to restriction of the enzyme to sequences from 6 to 17 amino acids. Therefore, the MDCK cell could be a very useful cellular model with which to study some of the suggested TOP biological functions as processing of biological active peptides and antigen presentation.

Amino Acid Sequence↗

Diagnosis of stroke by the nonneurologist. A validation study.

BACKGROUND AND PURPOSE: The first medical contact of an acute stroke victim is often a nonneurologist. Validation of stroke diagnosis made by these medical doctors is poorly known. The present study seeks to validate the stroke diagnoses made by general practitioners (GPs) and hospital emergency service physicians (ESPs). METHODS: Validation through direct interview and examination by a neurologist was performed for diagnoses of stroke made by GPs in patients under their care and doctors working at the emergency departments of 3 hospitals. RESULTS: Validation of the GP diagnosis was confirmed in 44 cases (85%); 3 patients (6%) had transient ischemic attacks and 5 (9%) suffered from noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in 169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most frequent conditions misdiagnosed as stroke were neurological in nature (cerebral tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo, 1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical disorders, 7). CONCLUSIONS: In the majority of cases, nonneurologists (either GPs or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke with drugs that do not cause serious side effects can be started before evaluation by a neurologist and CT scan.

Adult↗

[Prevalence of dyslipidemias in adult ambulatory laboratory tests from different health care providers].

OBJECTIVE: To detect differences in the prevalence of dyslipidemia in adult ambulatory laboratory tests from three different health care providers, in Salvador-Brazil, 1995. METHODS: The study was carried out using a probabilistic sample of 24 out of 104 laboratories (approximately equal to 25%) which performed the same enzymatic method for lipid tests with the same quality control. Laboratory tests results were separated into three groups, according to health care provider: Sistema Unico de Saúde (SUS, governamental), Health Maintenance Organizations (HMO), and Private or Patients Health Insurance (PHI). Criteria for dyslipidemias in mg/dl were: total cholesterol > or = 240; LDL-c > or = 160; HDL-c < 35 and triglycerides > or = 200. Prevalence rates, 95% confidence intervals (CI) and chi (2) test were used in the analysis. RESULTS: From the 5464 adult subjects, 14.8% were from SUS, 31.6%. from HMO and 53.6% PHI. The highest prevalence for hypercholesterolemia--28.0% (CI 24.0; 32.0) and for LDL-c > or = 160mg/dL--30.4% (CI 27.6; 33.2), were found in the HMO group. PHI had the highest prevalence for HDL-c < 35mg/dL--12.3% (CI 10.0; 13.8), and for hypertrygliceridemia--17.8% (CI 16.3; 19.3). Most of the differences among health providers were statistically significant. CONCLUSION: The best lypid profile observed in subjects from SUS suggests social differences in the prevalence of dyslipidemias. As compared to other dyslipidemias, HDL-c < 35mg/dL prevalence was lower than expected in all three groups. The data may provide insights to medical doctors and other health care professionals regarding the questions of dyslipidemias. It can also provide objective information to the patients and encourage them to change their life styles.

Adult↗

[Prevalence of dyslipidemias in adults in laboratory tests from Salvador, Brazil].

PURPOSE: To determine the prevalence of dyslipidemia in non-hospital laboratory tests of adults from Salvador, Brazil. METHODS: The study was carried out in subjects from a probabilistic sample of 25% of a total of 104 local laboratories that used the same enzymatic method for lipid analysis with the quality control as recommended by the Brazilian Society of Clinical Analyses. These represented 93% of all non-hospital laboratories of Salvador in 1995. The odd months of 1995 were selected for sampling in the present study. Criteria for dyslipidemias were: total cholesterol > or = 240; LDL > or = 160; HDL < 35 and triglycerides > or = 200 mg/dl. Prevalence rates and their 95% confidence intervals (CI) and chi 2 test were used in the analyses. RESULTS: Tests from two of the 26 laboratories were not used in the analyses due to file problems or refusal. 7,392 adults were screened, 65% female. We observed prevalence (95% CI) of hypercholesterolemia in 30.0 (27.8; 32.2)%, high LDL in 30.1 (30.8; 35.4)% and hypertriglyceridemia in 30.4 (29.0; 31.4)% of the females. As to the male subjects, prevalences were; 24.0 (20.5; 27.5)% for hypercholesterolemia, 26.1 (22.4; 29.3)% for high LDL, 27.6 (25.7; 29.5)% for hypertriglyceridemia. All gender differences were significant. Low HDL occurred in 15.9 (14.2; 17.8)% of males and in 8.0 (7.1; 8.9)% of females. CONCLUSION: Dyslipidemia is an important risk factor observed in non-hospital laboratory tests of men and women in Salvador. Our data may provide physicians and other health care professionals with objective information to encourage life-style changes.

Adult↗

Nutrient intakes of individuals from food-insufficient households in the United States.

OBJECTIVES: Understanding the nutritional consequences of food insufficiency is important for informed policy-making that addresses the problem of domestic hunger. This study estimated the extent to which individuals from food-insufficient households were likely to have low intakes of energy and 14 other nutrients. METHODS: The diets of pre-schoolers, adult women, and the elderly were analyzed with 24-hour recall data from the 1989 through 1991 Continuing Survey of Food Intake by Individuals. Logistic regression analysis was used to study the association of self-reported household food insufficiency with nutrient intakes below 50% of the recommended daily allowance. RESULTS: For adult women, food insufficiency was significantly associated with low intakes of eight nutrients, including energy, magnesium, and vitamins A, E, C, and B6. Elderly individuals in the food-insufficient group were also more likely to have low intakes of eight nutrients, including protein, calcium, and vitamins A and B6. Household food insufficiency was not significantly associated with low intakes among preschoolers. CONCLUSIONS: The results validate the use of self-reported hunger measures in nutritional surveillance and highlight nutrients of concern for food assistance and nutrition education efforts targeted at individuals from food-insufficient households.

Adult↗

Diagnosis of transient ischemic attack by the nonneurologist. A validation study.

BACKGROUND AND PURPOSE: Interobserver reliability of the diagnosis of transient ischemic attack (TIA) is low, and diagnosis of TIA made by nonneurologists is often erroneous. We sought to validate the diagnosis of TIA made by general practitioners (GPs) and by hospital emergency service physicians (emergency MDs). METHODS: A list of 20 neurological symptoms was distributed to 20 GPs and 22 neurologists who graded the compatibility of each symptom with the TIA diagnosis. At least two neurologists validated TIA diagnoses made by GPs for patients under their care or by emergency MDs. RESULTS: Compared with neurologists, GPs considered "confusion" and "unexplained fall" more often compatible with TIA and "lower facial palsy" and "monocular blindness" less often compatible with TIA. Validation of diagnosis by GP was confirmed in 10 patients (19%); 26 patients had strokes, and 16 (31%) had a noncerebrovascular disorder. Validation of diagnosis by emergency MD was confirmed in 4 patients (13%); 10 patients had strokes, and 17 (55%) had noncerebrovascular disorders. The most frequent conditions misdiagnosed as TIAs were transient disturbances of consciousness, mental status, and balance. CONCLUSIONS: The TIA concept is understood differently by neurologists and nonneurologists. GPs and emergency MDs often label minor strokes and several nonvascular transient neurological disturbances as TIAs. Until this misconception of TIA is changed, the term TIA should probably be avoided in the communication between referring physicians and neurologists. If not referred to a neurologist, one third to one half of patients labeled with a diagnosis of TIA will be inappropriately managed.

Cerebrovascular Disorders↗

Carotid stenosis associated with atrial fibrillation.

PURPOSE AND SETTING: To describe the prevalence and risk factors for carotid stenosis in TIA/stroke patients with non valvular atrial fibrillation (AF) and to compare clinical and CT characteristics of TIA/stroke in AF patients with and without carotid stenosis. SUBJECTS: 50 TIA/stroke patients with AF who had ultrasound investigation of the extracranial vessels, included in a prospective hospitalar registry. RESULTS: Twenty-two patients had some degree of carotid stenosis, but only 5 had more than 50% stenosis, including one with occlusion. Stenosis was neither more frequent nor more severe on the symptomatic side. Smokers were significantly more frequent in AF patients with > 50% stenosis. Clinical and CT features were quite similar in patients with and without carotid stenosis. CONCLUSION: The association in a TIA/Stroke patient of AF and severe carotid stenosis on the symptomatic side is exceptional. TIA/strokes related to carotid stenosis cannot be identified by their clinical/CT characteristics. Management of these patients must be decided by stratification of risk of recurrence for AF and from carotid stenosis and balance of these risks with that of endarterectomy.

Aged↗

A multivariate study of headache associated with ischemic stroke.

Thirty-four percent of 182 ischemic stroke patients registered during 1 year in a prospective hospital stroke data base complained of headache within a 72-hour interval of stroke onset. Headache was more common in patients under 70 years of age, in nonsmokers, in those with a past history of migraine, and in subjects presenting transient loss of consciousness, nausea/vomiting, or visual field defects. Headache was more frequent in vertebrobasilar (57%) than in carotid (20%) territory strokes, more so in posterior cerebral artery (90%) and cerebellar infarcts (80%), and was infrequent in subcortical infarcts (7%) and lacunes due to single perforator disease (9%). In multiple regression analysis, vertebrobasilar stroke (odds ratio 6.9), lacuanr stroke (odds ratio 0.06), and past history of migraine (odds ratio 6.7) were significant independent predictors of headache, suggesting that ischemic stroke location is the major determinant of stroke-associated headache, most probably related to activation of the trigeminovascular system, whose threshold may be modified by individual susceptibility.

Aged↗

Headache associated with transient ischemic attacks.

Sixty (29%) of 205 consecutive patients with transient ischemic attacks registered in a hospital stroke data base had headache within 72 hours of onset. Headache was significantly more common in nonsmokers (odds ratio = 2.8; 95% confidence interval = 6.7 to 1.2). Headache was infrequent in patients with amaurosis fugax, and was not significantly associated with any other particular clinical presentation of transient ischemic attack. Headache was more common in vertebrobasilar (33%) than in carotid distribution (24%) episodes, and was not rare in transient ischemic attacks presenting as lacunar syndromes (29%). Headache was less frequent in patients whose computerized tomograms showed an infarct appropriate to the symptoms (odds ratio = 0.2; 95% confidence interval = 0.02 to 1.4). A diffuse headache was more common in patients with lacunar events than in patients with cortical attacks (odds ratio = 3.0; 95% confidence interval = 13 to 0.07). No other association was found between headache location and the presumed involved vascular territory. Headache in patients with transient ischemic attacks is poorly related/explained by the clinical characteristics of the ischemic event.

Aged↗

Cerebrospinal fluid and therapy of isolated angiitis of the central nervous system.

BACKGROUND: Serial cerebral angiograms, computed tomography, and magnetic resonance imaging are among the proposed methods for monitoring disease activity and response to therapy in isolated angiitis of the central nervous system. Cerebrospinal fluid has not proved to be useful in monitoring clinical course. CASE DESCRIPTION: We describe a 45-year-old man with histological diagnosis of isolated angiitis of the central nervous system that was treated with prednisone plus azathioprine and monitored for 2 years. Samples of the cerebrospinal fluid were obtained for cytological and routine chemical examination, as well as albumin and immunoglobulin content. Before treatment, cerebrospinal fluid showed marked plasmatic transudation of albumin and intrathecal synthesis of immunoglobulins. During the first year of immunosuppression no events were noticed, and the previously abnormal aspects of the cerebrospinal fluid showed improvement. During the weaning of azathioprine, a new stroke occurred in conjunction with a marked deterioration of cerebrospinal fluid parameters. Immunosuppression was resumed at previous levels, and during the following year no further events occurred. Once again, abnormal cerebrospinal fluid values improved significantly. CONCLUSIONS: We report a case of isolated angiitis of the central nervous system in which the serial cerebrospinal fluid examinations (albumin and immunoglobulin content) showed a close correlation with clinical course. This method may be useful in monitoring response to therapy.

Albumins↗

Kluver-Bucy syndrome in systemic lupus erythematosus.

The Kluver-Bucy syndrome has not been previously reported as a complication of systemic lupus erythematosus (SLE). A 48-year-old female is described who sustained several cerebral infarcts, some of which were bitemporal, due to SLE vasculopathy. She developed a complex behavioural picture consisting of global aphasia, left-side neglect, hyperorality, hypermetamorphosis and hypersexuality. She displayed appropriate emotional reaction to visually presented objects, indicating that her Kluver-Bucy syndrome could not be explained by lack of visual recognition.

Aphasia↗

[Clinical pathology of the glomerulus--from phenomenon to entity. The mesangial lesion].

The numerous findings discussed lead to the following conclusions: 1. The mesangial lesions, which may take a wide range of different forms, can be classified into two groups according to whether an underlying immunological pathomechanism is involved. Those that result from such a pathomechanism represent various types of glomerulonephritis. 2. Amongst these immunologically-mediated glomerulonephritides mesangioproliferative glomerulonephritis (and, of this group, IgA nephritis) is the most common. Membranoproliferative glomerulonephritis is the most severe of these diseases. Either may be idiopathic or secondary, or may occur in association with systemic disease. 3. The number of macrophages in the mesangial lesions in glomerulonephritis correlates with the severity of the glomerulonephritis, the localization of the immune complex deposits and the degree of proteinuria. If the immune complex deposits extend out of the mesangium into the subendothelial space, the number of macrophages is higher, the structural changes are more marked, and proteinuria is more severe. 4. Various pathomechanisms and nosologic entities can lead to mesangial lesions of the type seen in mesangioproliferative glomerulonephritis or membranoproliferative glomerulonephritis. On the other hand, the same entity may be associated with mesangial lesions of different severity, and consequently the prognosis varies. Differential diagnosis of the mesangial lesions, which represent heterogeneous nosologic entities, requires the use of light microscopic, immunohistochemical, and electron microscopic techniques. Exact diagnosis is necessary because of the differences in prognosis. 5. The course and prognosis of mesangial lesions are determined by immunological and nonimmunological factors. Long-term studies have demonstrated that prognostically relevant information can already be gained at the time of biopsy by the assessment of certain morphological features (e.g., immunohistological findings, severity of glomerulonephritis, the presence of focal/segmental lesions) and clinical parameters (e.g., proteinuria, hematuria, hypertension, and serum creatinine concentration). The decisive predictor of an unfavorable prognosis is the presence of interstitial fibrosis.

Glomerular Mesangium↗