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Biomedical subjects

A Pinto

Publications and source records attributed to A Pinto.

At least 397 records · Page 22Linked to original sources
PubMedDate not supplied

Identification of new Fas mutations in a patient with autoimmune lymphoproliferative syndrome (ALPS) and eosinophilia.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare, newly recognized, chronic lymphoproliferative disorder in children and is characterized by lymphadenopathy, splenomegaly, pancytopenia, autoimmune phenomena and expansion of double-negative (DN) T lymphocytes (TCR alpha beta+, CD4-, CD8-). Defective lymphocyte apoptosis caused by mutations of the Fas (CD95) gene has been linked in the pathogenesis of ALPS, as binding of Fas-ligand to Fas can trigger apoptosis. Of the ALPS cases reported to date, point mutations, frameshifts and silent mutations in Fas all have been identified. We report two new point mutations in Fas in a child with ALPS and eosinophilia; studies on other family members established the pattern of inheritance for these mutations. Flow cytometric analysis of blood and tissues (spleen, lymph node, bone marrow) revealed abnormally expanded populations of DN T lymphocytes. Furthermore, activated lymphocytes and IFN gamma-activated eosinophils were resistant to Fas-mediated apoptosis. Eosinophil resistance to Fas-mediated apoptosis has not been previously described in ALPS. Sequencing of Fas revealed two separate mutations not previously reported. One mutation, a C to T change at base 836, was a silent mutation inherited from the mother, while the second mutation, a C to A change at base 916, caused a non-conservative amino acid substitution in the death domain of Fas, changing a threonine to a lysine. This mutation is associated with a predicted change in the structure of a part of the death domain from a beta-pleated sheet to an alpha-helix. We speculate that the mutation in the death domain prevents the interaction of Fas with intracellular mediators of apoptosis and is responsible for the autoimmune manifestations of ALPS and the abnormal lymphocytosis and eosinophilia in this patient.

Adult↗
PubMedDate not supplied

The inhibition of platelet aggregation by activated macrophages is blocked by dexamethasone.

The effect of dexamethasone on the ability of activated J774 macrophages to inhibit platelet aggregation was investigated. After 24h incubation with lipopolysaccharide and gamma-interferon, J774 cells generated large amounts of nitric oxide and inhibited platelet aggregation. Incubation of the cells with dexamethasone (0.01-10 microM) caused a concentration-dependent inhibition of both the NO2- production and the anti-aggregating activity of the cells. The inhibitory effect of dexamethasone was blocked by the glucocorticoid antagonist RU 38486. These data suggested that the protective effect of glucocorticoids in endotoxin-induced hypotension and their immunosuppressive action may both depend, at least in part, on the inhibition by these steroids of the induction of the nitric oxide synthase.

Animals↗
PubMedDate not supplied

Varying role of alpha/beta interferon in the antiviral efficacy of synthetic immunomodulators against Semliki Forest virus infection.

The question of whether interferon alpha/beta is the common mechanism of antiviral action of synthetic immunomodulators was investigated in B6C3F1 mice infected with Semliki Forest virus. Mice were treated with various concentrations of normal sheep serum or potent anti-alpha/beta interferon antiserum, inoculated with the immunomodulators, and infected 24 hours later with virus. Three patterns emerged. The antiviral action of the pyrimidinone (ABMP) and the oral interferon inducer (CL246,738) appeared to be mediated primarily by interferon alpha/beta; their protective ability was almost completely abrogated by treatment with low levels of anti-alpha/beta interferon antiserum. The antiviral action of two other immunomodulators, a mismatched polyribonucleotide (Ampligen) and a polyanionic copolymer (MVE-2) at least partially involved interferon. Activity of these compounds was reduced, but not consistently eliminated by treatments with high doses of antiserum. The antiviral activity of another polyribonucleotide, polyriboinosinic-cytidylic acid complexed with lysine carboxymethylcellulose (poly ICLC), was not affected by treatment with even the highest amount of antiserum (two injections of 100,000 neutralizing units each). Almost complete protection by poly ICLC was observed despite the fact that this high concentration of antiserum, when given alone, caused a decrease in natural resistance to Semliki Forest virus infection. Taken together, these results indicate that induction of interferon alpha/beta does not appear to be the major common mechanism of antiviral activity among these diverse synthetic immunomodulators.

Acridines↗
PubMedDate not supplied

Overweight and obesity in children and adolescents: relationship with blood pressure, and physical activity.

OBJECTIVE: Using body mass index (BMI) quartiles, the present study's aims were (1) to describe and evaluate the relationship between overweight/obesity with cardiovascular disease (CVD) risk factors, such as systolic blood pressure (SBP), diastolic blood pressure (DBP) and physical activity; (2) to provide information on the prevalence of high blood pressure and physical activity according to BMI quartiles; and (3) to examine the relationship of risk of obesity to adverse levels of high blood pressure and physical activity. METHODS: The sample consisted of 1439 children (758 males and 681 females), 8-16 years old. Participants were classified as being at 'risk of obesity' according to age- and sex-adjusted fourth quartile of BMI values. Blood pressure was measured using the Dinamap monitor. An adapted version of the Weekly Activity Checklist was applied for the diagnosis of physical activity index (PAI). RESULTS: Systolic and diastolic blood pressures were significantly (p < 0.05) and positively related to BMI, whereas no significant associations were reported between BMI and PAI in both genders. Overall, the proportion of subjects with adverse levels of blood pressure (SBP or DBP) ranged from 21.3% in the first BMI quartile (BMI-1Q) to 30.4% in BMI-4Q (p < 0.05). The PAI ranged from 24.5% in BMI-1Q to 20.6 in BMI-4Q and no significant differences were found. Children and adolescents at 'risk of obesity' were 1.5 times as likely to have at least one risk factor (high blood pressure or low level of activity). CONCLUSIONS: Our data suggest that higher BMI is associated with higher values of SBP and DBP. Children and adolescents in the upper quartile of BMI are 1.5 times as likely to have at least one risk factor. Furthermore our data confirmed previous findings that higher levels of BMI are associated with a unfavourable risk profile for CVD risk factors.

Adolescent↗
PubMedDate not supplied

Neutrophil depletion suppresses 111In-labeled platelet accumulation in infarcted myocardium.

Platelets and neutrophils accumulate rapidly in infarcted myocardium. Although antineutrophil agents reduce the size of the infarcted area, this is not observed with antiplatelet drugs. The possibility that myocardial ischemia-induced platelet deposition was secondary to a neutrophil-mediated event was assessed by injecting prostacyclin-washed autologous 111In-labeled platelets and measuring the amount of radioactivity in different regions of the heart following 90-min occlusion of the left anterior descending coronary artery followed by reperfusion for periods up to 5 h. Platelet deposition during the reperfusion phase was linear with time and similar to the time course of neutrophil accumulation. There was a transmural distribution of radioactivity across the myocardium where the "zone" between infarcted and risk regions, called the "interface," greater than infarct greater than risk greater than normal. Neutropenia (21 +/- 2% control levels), induced with specific sheep anti-dog neutrophil antiserum, had minimal effects on platelet aggregation ex vivo, but significantly reduced platelet accumulation in the ischemic myocardium following 5-h reperfusion and abolished the transmural platelet distribution. These results suggest that myocardial platelet deposition is secondary to a neutrophil-mediated event in this occlusion-reperfusion model of myocardial injury. Interactions between platelets and neutrophils at the site of tissue damage may influence the process of myocardial ischemic injury.

Animals↗
PubMedDate not supplied

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Cytochrome P-450-dependent mixed function oxidase activity is present in vascular tissue; however, as far as we could determine, the distribution of monooxygenase activity across the blood vessel wall has not previously been assessed. The aryl-hydrocarbon hydroxylase activity was examined by metabolism of benzo[a]pyrene in microsomes prepared from intimal and smooth muscle cell scrapings of the hog thoracic aorta. Microsomes of intimal cells comprising 95% endothelial cells showed an approximately 2.5-fold increase in aryl-hydrocarbon hydroxylase activity compared with that in microsomes prepared from medial smooth muscle cells. Michaelis-Mentin kinetics for the intimal enzyme yielded an apparent Km value of 11.11 microM and an apparent Vmax of 3-OH benzo[a]pyrene of 40 pmol/mg protein/10 min. Aryl-hydrocarbon hydroxylase activity was dependent on nicotinamide adenine dinucleotide phosphate and was inhibited by 7,8 benzoflavone, SKF 525A, and carbon monoxide. The localization of cytochrome P-450-dependent mixed function oxidase primarily to the intimal surface of the aorta may indicate a role for this enzyme system in vasoregulation and the pathogenesis of atherosclerosis.

Animals↗
PubMedDate not supplied

Parenteral nutrition in cancer patients receiving chemotherapy: effects on toxicity and nutritional status.

The role of total parenteral nutrition (TPN) in reducing toxicity related to cancer chemotherapy (CT) is presently a controversial issue. To evaluate the effectiveness of TPN in reducing CT-associated toxicity and correcting and preventing CT-related impairments of nutritional status, a prospective crossover controlled study was performed in 43 cancer patients (19 normally nourished and 24 malnourished) randomly divided into two groups (A and B). Group A patients received TPN concomitantly with the first course of chemotherapy, and the second course was administered 21 to 28 days later without TPN support; group B patients were treated in the opposite sequence. The rates of myelotoxicities and gastrointestinal toxicities after CT courses with or without TPN were essentially similar in normally nourished and malnourished patients. No changes in nutritional indexes were detected in normally nourished subjects after each course. Conversely, in undernourished subjects, prealbumin, retinol-binding protein, and nitrogen balance increased in CT+TPN courses (p < .02). In CT-only courses, undernourished subjects showed a decrease in prealbumin and nitrogen balance. Significant changes of nitrogen balance in CT vs CT+TPN courses were detected in malnourished subjects. TPN appears to be unable to reduce CT-associated toxicity. CT administration does not result in any impairment of the nutritional status in normally nourished cancer patients. From our study, it appears that TPN should be limited to severely malnourished neoplastic patients undergoing CT, because of its ability to prevent further impairment of nutritional status and to improve the nitrogen balance and the levels of fast-turnover visceral proteins.

Adult↗
PubMedDate not supplied

Immunoinflammatory activation during the acute phase of lacunar and non-lacunar ischemic stroke: association with time of onset and diabetic state.

Several studies have stressed the involvement of inflammation in the pathophysiology of acute brain ischemia, but the role of immunoinflammatory activation in diabetic stroke patients has not yet been fully evaluated. The aim of our study was to evaluate immunoinflammatory activation of acute phase of stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute ischemic stroke and 123 subjects without acute ischemic stroke, and measured levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM-1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24-72h. Our stroke patients exhibited significantly higher plasma levels of cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones. Lacunar strokes in comparison with those non-lacunar exhibited significantly lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic patients with lacunar strokes exhibited a minor grade of immunoinflammatory activation of the acute phase at 24-72h and 7-10 days after stroke onset. The minor grade of immunoinflammatory activation of patients with lacunar strokes, particularly diabetic ones, could be related to the minor extension of the infarct size, owing to the typical microvascular disease of diabetic subjects which could also explain the reported better outcome of this subtype of ischemic stroke.

Acute Disease↗
PubMedDate not supplied

Fate of pesticides in tropical soils of Brazil under field conditions.

The potential of pesticides for nonpoint ground water pollution depends on their dissipation and leaching behavior in soils. We investigated the fate of 10 pesticides in two tropical soils of contrasting texture in the Brazilian Cerrado region near Cuiabá during an 80-d period, employing topsoil dissipation studies, soil core analyses, and lysimeter experiments. Dissipation of pesticides was rapid, with field half-lives ranging from 0.8 to 20 d in Ustox and 0.6 to 11.8 d in Psamments soils. Soil core analyses showed progressive leaching of polar pesticides in Psamments, whereas in Ustox pesticides were rapidly transported to 40 cm soil depth regardless of their sorption properties, suggesting that leaching was caused by preferential flow. In lysimeter experiments (35 cm soil depth), cumulative leaching was generally low, with < or = 0.02% and < or = 0.19% of the applied amounts leached in Ustox and Psamments, respectively. In both soils, all pesticides but the pyrethroids were detected in percolate at 35 cm soil depth within the first 6 d after application. Cumulative efflux and mean concentrations of pesticides in percolate were dosely correlated with their Groundwater Ubiquity Score (GUS). The presence of alachlor (2-chloro-2', 6'-diethyl-N-methoxymethylacetanilide), atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine), metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide], simazine [2-chloro-4,6-bis(ethylamino)-1,3,5-triazine], and trifluralin (2,6-dinitro-N,N-dipropyl-4-trifluoromethylaniline) throughout the soil profile and in percolate of wick lysimeters at 95 cm soil depth indicated that a nonpoint pollution of ground water resources in tropical Brazil cannot be ruled out for these substances.

Agriculture↗
PubMedDate not supplied

[Personal experience in 71 consecutive patients with acute cholecystitis].

PURPOSE: Acute cholecystitis is one of the most frequent abdominal inflammatory processes. If untreated or misdiagnosed it can result in severe complications such as gallbladder rupture, abscesses, or peritonitis. We retrospectively reviewed a series of 71 consecutive patients with surgical confirmation of acute cholecystitis and now compare the results of the diagnostic techniques we used preoperatively. MATERIAL AND METHODS: Over 16 months, 71 consecutive patients (42 women and 29 men; age range: 34-84 years, mean: 58) with acute abdominal pain were operated on for acute cholecystitis at Cardarelli Hospital, Naples. Abdominal plain film was performed in 65 of 71 cases, abdominal US in 69 and abdominal CT in 6. On abdominal plain films, we retrospectively searched the following signs: densities projected over the gallbladder, linear calcifications in gallbladder walls, gallbladder enlargement, focal gas collections within the gallbladder, and air-fluid levels in the gallbladder lumen. On US images we looked for: gallbladder wall thickening (> 3 mm), intraluminal content in the gallbladder, pericholecystic fluid, US Murphy's sign, and gallbladder distension. On CT images, we investigated: gallbladder distension, wall thickening, intraluminal content, pericholecystic fluid, and inflammatory changes in pericholecystic fat. Associated complications of cholecystitis were also searched on all images. RESULTS: On plain abdominal films we found densities projected over the gallbladder (16.9%) and linear calcifications in the gallbladder wall (4.6%). Abdominal US demonstrated gallbladder wall thickening (56.5%), one or more gallstone(s) (85.5%), pericholecystic fluid (14.5%), gallbladder distension (46.4%), and US Murphy's sign (39.1%). Abdominal CT showed gallbladder wall thickening (83.3%), gallbladder distension (66.6%), pericholecystic fluid (66.6%), gallstones (50%), inflammatory changes in pericholecystic fat (33.3%), and increased bile density (> 20 HU) (33.3%). CONCLUSIONS: US appears to be the most useful imaging technique in patients with suspected acute cholecystitis, for both screening and final diagnosis. CT plays a limited role in the early assessment of these patients, but can be a useful tool in diagnosing acute cholecystitis in patients with questionable physical findings or in investigating related complications.

Acute Disease↗
PubMedDate not supplied

Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure.

Thirty patients aged 65-85 years, with refractory New York Heart Association (NYHA) class IV congestive heart failure (CHF) were treated with an intravenous infusion of furosemide (250-2000 mg/d) and small-volume hypertonic saline solution (150 mL of 1.4-4.6% NaCl) twice a day for 6 to 12 days. A daily fluid oral intake of 1000 mL and previous cardiac therapy were maintained. Clinical signs and symptoms of CHF, such as dyspnea, edema and weakness, improved, as did severity of illness as defined by NYHA class. The infusion was well tolerated. After a 12-month follow-up, 24 patients (80%) were alive and in the NYHA class assigned on discharge from the hospital. This therapeutic combination is effective and well tolerated and should represent an innovative approach to the management of refractory CHF.

Aged↗