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Biomedical subjects

M Silva

Publications and source records attributed to M Silva.

At least 73 records · Page 4Linked to original sources
PubMed1998

Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene.

Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lpsd allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4. Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact.

Amino Acid Sequence↗
PubMed1998

The effect of protease inhibitors on weight and body composition in HIV-infected patients.

OBJECTIVES: To determine the nutritional changes that occur in HIV-infected patients receiving protease inhibitor (PI) therapy and to determine the effects of PI treatment on physical functioning and health perceptions in patients with HIV infection. DESIGN: Longitudinal data analysis of 38 patients from a large Nutrition and HIV cohort. METHODS: Patients were included if they had started PI therapy after enrollment in the cohort, if they had taken the drug for at least 4 months without interruption and if data on weight, body composition and viral loads were available. RESULTS: Mean person-months of follow-up was 8.1 months before and 12.2 months after PI treatment. Weight (1.54 kg, P < 0.0001), body mass index (0.50 kg/m2, P < 0.0001), physical functioning (8.52 points, P = 0.0006) and current health perception (6.7 points, P = 0.01) increased significantly, and the daily caloric intake increase was close to significance (915.5 kJ/day, P = 0.06), after treatment with PI. Lean body mass did not change. Patients who responded to PI therapy with decreased viral load (n = 28) had significantly greater weight gain per month than non-responders. CONCLUSIONS: PI therapy of HIV infection is associated with weight gain and improvement in quality of life indices. The weight gain is mainly in fat mass, with no change in lean body mass (skeletal muscle). Optimal therapy of HIV-infected patients with weight loss may require highly active antiretroviral therapy combined with an anabolic stimulus such as exercise, anabolic steroids or human growth hormone.

Adult↗
PubMed1998

Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2.

A series of nonpeptide somatostatin agonists which bind selectively and with high affinity to somatostatin receptor subtype 2 (sst2) have been synthesized. One of these compounds, L-054,522, binds to human sst2 with an apparent dissociation constant of 0.01 nM and at least 3,000-fold selectivity when evaluated against the other somatostatin receptors. L-054,522 is a full agonist based on its inhibition of forskolin-stimulated adenylate cyclase activity in Chinese hamster ovary-K1 cells stably expressing sst2. L-054,522 has a potent inhibitory effect on growth hormone release from rat primary pituitary cells and glucagon release from isolated mouse pancreatic islets. Intravenous infusion of L-054,522 to rats at 50 microgram/kg per hr causes a rapid and sustained reduction in growth hormone to basal levels. The high potency and selectivity of L-054, 522 for sst2 will make it a useful tool to further characterize the physiological functions of this receptor subtype.

Animals↗
PubMed1998

Expression of Bcl-x in erythroid precursors from patients with polycythemia vera.

BACKGROUND: Deregulating the expression of Bcl-xL, an inhibitor of apoptosis, in an erythropoietin-dependent erythroblast cell line averts apoptosis induced by the withdrawal of erythropoietin. Since in polycythemia vera an abnormal clone of erythroid progenitors is independent of erythropoietin, we investigated whether the endogenous expression of Bcl-xL was deregulated in these cells. METHODS: Erythroid colonies from patients with polycythemia vera and normal subjects were cultured in the presence and absence of erythropoietin and assessed by immunocytochemical and flow-cytometric analysis with anti-Bcl-x antibodies that recognize the two species of Bcl-x (Bcl-xL and Bcl-xS). Reverse-transcriptase-polymerase-chain-reaction analysis was used to determine which one of the two species was responsible for anti-Bcl-x staining. Bone marrow mononuclear cells from 8 healthy bone marrow donors, 14 patients with polycythemia vera, 19 patients with other myeloproliferative syndromes, and 12 patients with secondary erythrocytosis were analyzed by flow cytometry with antibodies against Bcl-x and glycophorin A, an erythroid marker. RESULTS: Erythroid cells from patients with polycythemia vera survived in vitro without erythropoietin, and this finding correlated with the expression of Bcl-x protein (Bcl-xL messenger RNA was the main species of Bcl-x found), even in mature erythroblasts that normally do not express Bcl-x. The mean (+/-SD) percentage of cells positive for both glycophorin A and Bcl-x in the 14 patients with polycythemia vera (21.8+/-3.6 percent) was significantly higher than that in 8 normal donors (6.62+/-1.58 percent), 12 patients with secondary erythrocytosis (6.87+/-1.95 percent), 9 patients with essential thrombocythemia (3.81+/-0.97 percent), and 10 patients with chronic myeloid leukemia (2.7+/-0.41 percent). CONCLUSIONS: Deregulated expression of Bcl-x may contribute to the erythropoietin-independent survival of erythroid-lineage cells in polycythemia vera and thereby contribute to the pathogenesis of this disease.

Adolescent↗
PubMed1998

Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region.

On the basis of 2093 meioses analyzed in two separate intraspecific backcrosses, the location of the mouse Lpsd mutation was circumscribed to a genetic interval 0.9 cM in size. A total of 19 genetic markers that lie in close proximity to the mutation were examined in mapping. Most of these were previously unpublished polymorphic microsatellites, identified by fragmentation of YAC and BAC clones spanning the region of interest. Lpsd was found to be inseparable from the microsatellite marker D4MIT178, and from three novel polymorphic microsatellites identified near D4MIT178. The mutation was confined between two novel microsatellite markers, herein designated "B" and "83.3." B lies centromeric to the mutation, and was separated by four crossovers in a panel of 1600 mice; 83.3 lies distal to the mutation and was separated by three crossovers in a panel of 493 mice. 66 BAC clones and one YAC clone were assembled to cover > 95% of the critical region. Estimates based on pulsed field gel electrophoresis and fluorescence in situ hybridization indicate that the The B-->83.3 interval is about 3.2 Mb in length. A minimal area of zero recombinational distance from Lpsd was also assigned, and found to occupy approximately 1.2 Mb of physical size. To identify gene candidates, nearly 40,000 sequencing runs were performed across the critical region. Selective hybridization and exon trapping were also employed to identify genes throughout the "zero" region. Only a single intact gene was identified within the entire critical region. This gene encodes the Toll-4 receptor, a member of the IL-1 receptor family.

Animals↗
PubMed1998

Endocardial and epicardial ablation guided by nonsurgical transthoracic epicardial mapping to treat recurrent ventricular tachycardia.

INTRODUCTION: An epicardial site of origin of ventricular tachycardia (VT) may explain unsuccessful endocardial radiofrequency (RF) catheter ablation. A new technique to map the epicardial surface of the heart through pericardial puncture was presented recently and opened the possibility of using epicardial mapping to guide endocardial ablation or epicardial catheter ablation. We report the efficacy and safety of these two approaches to treat 10 consecutive patients with VT and Chagas' disease. METHODS AND RESULTS: Epicardial mapping was carried out with a regular steerable catheter introduced into the pericardial space. An epicardial circuit was found in 14 of 18 mapable VTs induced in 10 patients. Epicardial mapping was used to guide endocardial ablation in 4 patients and epicardial ablation in 6. The epicardial earliest activation site occurred 107+/-60 msec earlier than the onset of the QRS complex. At the epicardial site used to guide endocardial ablation, earliest activation occurred 75+/-55 msec before the QRS complex. Epicardial mid-diastolic potentials and/or continuous electrical activity were seen in 7 patients. After 4.8+/-2.9 seconds of epicardial RF applications, VT was rendered noninducible. Hemopericardium requiring drainage occurred in 1 patient; 3 others developed pericardial friction without hemopericardium. Patients remain asymptomatic 5 to 9 months after the procedure. Interruption during endocardial pulses occurred after 20.2+/-14 seconds (P = 0.004), but VT was always reinducible and the patients experienced a poor outcome. CONCLUSION: Epicardial mapping does not enhance the effectiveness of endocardial pulses of RF. Epicardial applications of RF energy can safely and effectively treat patients with VT and Chagas' disease.

Adult↗
PubMed1998

[Type I atrial flutter radiofrequency ablation. Importance of bidirectional block of isthmus between the inferior vena cava and of tricuspid valve ring].

PURPOSE: To determine the clinical importance of a bi-directional line of block demonstration in the inferior vena cava-tricuspid annulus isthmus as an end-point for radiofrequency (RF) atrial flutter (FL) ablation. METHODS: Forty consecutive patients (51 +/- 11 years) with type I FL were divided in 2 groups: GI (30 patients) anatomic, non-electrophysiologic isthmus ablation technique (interruption and non-induction FL criteria); and GII (10 patients) anatomic with electrophysiologic evaluation of bi-directional isthmus conduction. The isthmus activation was analyzed before and after anatomic RF ablation with a cateter exploring each side of the line of block, depending on the conduction evaluation (anterograde or retrograde). RESULTS: FL was interrupted and not reinduced in 26/ 30 (86.6%) GI patients and in 10 (100%) GII patients (p = 0.5558). During follow-up FL recurred in 30% of the patients in both groups. In GII, 6 patients with bi-directional block remained assymptomatic, whereas 3 patients with unidirectional block presented recurrence (p = 0.012). CONCLUSION: Electrophysiologic demonstration of bidirectional line of block in the isthmus is related to long-term success and should be the criterion for interruption of type I atrial FL RF ablation.

Atrial Flutter↗
PubMed1998

The changing focus of nursing practice in Brazil.

Using a historical-social perspective, the authors aim at understanding and analysing the vision of supervision and leadership in the history of Brazilian nursing from 1930 to 1995. The empirical material comprised journal articles, books, theses and proceedings. In the first period (1930-1949), preliminary expressions of the organization and control of nursing work were found. In the second (1950-1969), the concept of human relations at work emerged in the third period (1970-1979) evidence was found for concern about staffing structures following changes in the health sector. In the most recent period (1980-1995), a new perspective is established, emphasising nursing as a social practice related to supervision rather than leadership. Based on this historical search, and linked with views of health practice and change in Brazilian society, supervision and leadership can be located within management ideas and practice. These concepts are understood, generally, within a theoretical critique that should demonstrate a close relationship with control of workers or the work process and its effects in the health sector, especially in nursing.

Brazil↗
PubMed1998

Pathogenesis of polycythemia vera.

BACKGROUND AND OBJECTIVE: Polycythemia vera (PV) is an acquired clonal myeloproliferative disorder characterized by increased production of mature red cells. We still lack a molecular target responsible for this disorder; however, recent investigations have focused on a number of molecules involved in signal transduction pathways mediated by erythropoietin (Epo) and other growth factors. Here we review the implication of these molecules in the pathogenesis of PV. INFORMATION SOURCES: The material reviewed in this work includes articles published in journals covered by Medline. We also include data obtained in our laboratory regarding to the significance of apoptosis inhibitory proteins in erythroid development. STATE OF THE ART AND PERSPECTIVES: Overproduction of erythroid cells in PV is particular in that it occurs in the absence of a recognizable physiologic stimulus, since circulating serum levels of Epo are normal or lower than normal. Genetic analysis as well as in vitro studies, have established an essential role for Epo in the survival and maturation of committed erythroid progenitors. Epo initiates its cellular response by binding to the Epo receptor (EpoR) expressed on the surface of immature erythroblasts. Following ligand binding, EpoR is known to activate a cytoplasmic protein tyrosine kinase, Jak2 which triggers a signal transduction cascade that leads to the development of early erythroid progenitors into mature erythroblast cells. Although the mechanism underlying the increased erythroid production in PV is not well understood, a number of causes have recently came for which may provide insights not only for the pathogenesis of PV but also for a fundamental biological process: the mechanism whereby a multipotential stem cell gives rise to a particular cell lineage.

Animals↗
PubMed1998

[Use of transjugular intrahepatic portosystemic shunt (TIPS) in an 84 year-old patient during acute variceal bleeding].

The transjugular intrahepatic protosystemic shunt (TIPS) is a nonsurgical method with low mortality which does not interfere with subsequent liver transplantation. We describe the case of an old male patient with chronic hepatopathy who was admitted because of an episode of variceal bleeding. Due to the failure of the medical treatment and sclerotherapy, coronarian stomachic vein was embolized with a coil and a TIPS was performed during the acute episode of variceal bleeding. He evolved favorably and after a year of the procedure remains asymptomatic.

Acute Disease↗
PubMed1997

The expression of Bcl-x is downregulated during differentiation of human hematopoietic progenitor cells along the granulocyte but not the monocyte/macrophage lineage.

Expression of the apoptosis inhibitory protein Bcl-x was studied in CD34+ hematopoietic precursor cells and in the promyelocytic leukemia cell line HL-60. The enriched population of CD34+ cells (more than 95%) was cultured in the presence of stem cell factor, interleukin-3 (IL-3), IL-6, and either granulocyte colony-stimulating factor or macrophage colony-stimulating factor to achieve granulocyte or monocyte/macrophage differentiation, respectively. The expression of Bcl-x increased in the early stages of both differentiation pathways. However, by day 21 of culture mature granulocytes were Bcl-x-negative, whereas monocytes/macrophages either maintained or increased the expression of Bcl-x. The pattern of Bcl-x expression in the differentiated CD34+ cells was similar to that observed in HL-60 cells differentiated along the granulocyte lineage (induced by incubation with retinoic acid), or along the monocyte/macrophage lineage (induced by incubation with phorbol diester). The bcl-x transcript predominant in HL-60 and CD34+ cells differentiated into monocytes/macrophages was bcl-xL. Although little is yet known regarding the functional significance of Bcl-x within the granulomonocytic compartment, marked changes in the pattern of its expression, as observed during granulomonocytic differentiation of HL-60 and CD34+ cells, are likely to alter the life span of mature granulocytes and monocytes/macrophages.

Antigens, CD↗
PubMed1997

Adenoviral vectors given intravenously to immunocompromised mice yield stable transduction of the colonic epithelium.

BACKGROUND & AIMS: Adenoviral vectors have been used for gene transfer in the liver but not for gene transfer in intestinal tissue. The aim of this study was to show that in selectively immunocompromised mice injected intravenously with a recombinant adenovirus, higher levels of a reporter gene are expressed in the colon than in the liver. METHODS: Adenovirus encoding beta-galactosidase was injected intravenously in lethally irradiated B6D2F1 mice that had received syngeneic B6D2F1 bone marrow and spleen cell transplants, in athymic mice, in mice treated with 2-chlorodeoxyadenosine, or in normal mice. Enzymatic assays and polymerase chain reaction analysis were performed on colonic tissue obtained months after transduction. Colonic tissues were also stained for beta-galactosidase. RESULTS: Intravenous adenoviral administration yielded long-term expression of a foreign gene in liver and colonic epithelium in transiently immunocompromised recipients. Histological analysis suggested that stem cell transfection and integration of the foreign gene may have occurred insofar as crypts and colonic epithelial cells in immunocompromised animals stained positive for beta-galactosidase months after virus administration. In polymerase chain reaction analysis, the transverse and distal colon of syngeneic bone marrow transplant recipients showed long-term retention of beta-galactosidase gene. CONCLUSIONS: Long-term transduction of colonic epithelial cells is observed after administration of adenoviral vectors by an intravenous route in selectively immunocompromised mice.

Adenoviridae↗
PubMed1997

Immunodiagnosis of fasciolosis in horses and pigs using western blots.

Crude and partially purified somatic (S) and excretory-secretory (ES) antigens of Fasciola hepatica were subjected to Western blot analysis in order to identify polypeptides that would enable specific and sensitive immunodiagnosis of horse and pig fasciolosis to be undertaken. Sera from 20 horses and 20 pigs with natural infections of F. hepatica and the same number of uninfected hosts of each species were tested, together with sera from 2 pigs with Cysticercus cellulosae infections. Using crude S antigens, sera from infected horses and pigs reacted specifically with a wide range of polypeptides of 14-19, 22-30, 35-37 and 42 kDa. Likewise, specific reactivity between polypeptides of 14-17, 22-30 and 40-42 kDa in crude ES antigens and sera from infected horses and pigs was obtained. Against the criteria of high sensitivity and specificity, the 22-30-kDa polypeptides would appear to be the most suitable candidate antigens for use in the immunodiagnosis of fasciolosis in horses and pigs.

Animals↗
PubMed1997

Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler sonographic screening in a large family.

BACKGROUND/AIMS: The prevalence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia has been estimated in the literature on clinical criteria, thus giving unreliable data. In our study the presence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia was evaluated in a large Italian family by using Doppler sonography findings were compared to computed tomography and angiography results. Clinical features were related to the severity of hepatic vascular malformations. METHODS: Seventy-three relatives were checked for the presence of signs of hereditary hemorrhagic telangiectasia. Abdominal Doppler ultrasonography was performed in all of them. Every subject with a positive Doppler ultrasonography for hepatic vascular malformations underwent abdominal computed tomography and celiac angiography. RESULTS: Forty family members proved to be affected by hereditary hemorrhagic telangiectasia. Of these, hepatic vascular malformations were evidenced by Doppler ultrasonography in 13 females. Doppler ultrasongraphy demonstrated minimal hepatic vascular abnormalities in three subjects, moderate in three, and severe in seven. Doppler study was diagnostic for arteriovenous shunt with hepatic veins in seven cases and with portal vein in two. Computed tomography failed to demonstrate hepatic vascular malformations in two cases, while angiography confirmed the Doppler sonographic findings in all cases. Cholestasis was present in subjects with moderate and severe hepatic vascular malformations. CONCLUSIONS: Doppler sonography is the ideal imaging technique to screen hereditary hemorrhagic telangiectasia affected families for hepatic vascular malformations. These malformations do not appear to be age-dependent, but sex-dependent. Cholestasis is the main clinical sign, and it seems to correlate with the severity of hepatic vascular derangement.

Adolescent↗
PubMed1997

Carotid arterial trauma: assessment with the Glasgow Coma Scale (GCS) as a guide to surgical management.

Management of carotid arterial injuries associated with focal neurological deficit or altered state of consciousness (SCON) remains unresolved. Experience with these injuries in one particular hospital was reviewed and the Glasgow Coma Scale (GCS) utilized to assist with clinical stratification of these patients. A literature review was also conducted to better define indications for repair or ligation of carotid injuries. From 1978 to 1990, 34 patients with carotid arterial injuries were reviewed with reference to the GCS, focal deficit, hypotension, anatomic site and mechanism of injury. The literature from 1952 to 1993 was surveyed for carotid artery injuries (1316 patients). Outcome of treatment with or without repair was compared with pre-operative neurologic status. Thirty-four patients with injuries of the common (24) or internal (10) carotid arteries were managed with repair (68%), ligation (24%) or observation (9%). The SCON was normal in 18 patients; 16 patients (88%) underwent repair and all remained normal. All patients with GCS 9-14 regained a normal SCON after surgical repair, while 10 patients with GCS < 8 had repair (5), ligation (3), and non-operative management (2); five returned to normal, four died and one remained comatose. However, outcomes correlated poorly with management. Of 1316 patients cited in the surgical literature, patients with no deficit and patients with pre-operative deficits did significantly better after repair as compared with ligation (P<0.001). In comatose patients, management did not affect outcome. It is concluded that carotid arterial injuries should be repaired in patients with normal neurologic evaluation, focal pre-operative neurologic deficits and in patients with GCS > 9. Comatose patients with GCS < 8 do poorly regardless of management. The GCS provides an objective for stratification of patients with altered SCON who benefit from repair of carotid arterial injuries.

Adult↗