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Biomedical subjects

A Ribeiro

Publications and source records attributed to A Ribeiro.

At least 73 records · Page 4Linked to original sources
PubMed1994

The effects of thalidomide treatment on autoimmune-prone NZB and MRL mice are consistent with stimulation of the central immune system.

We describe here some immunomodulatory effects of thalidomide on autoimmune-prone mice. The highly increased synthesis of splenic IgM in NZB mice, of splenic and lymph node IgG of different subclasses in MRL/n mice, and of splenic and lymph node IgG1 in MRL/lpr mice was markedly inhibited by thalidomide treatment. After a single treatment with 3 mg of thalidomide, the following changes were observed in NZB mice: (i) an initial decrease in the numbers of large CD5+ microhigh, and in the numbers of total CD5+ micro-, CD5- microhigh, CD5+ microhigh lymphocyte populations of the pleural cavity followed by a late increase in the numbers of large cells of the three cell populations; (ii) a consistent increase in the numbers of a CD5low microlow pleural lymphoid population; (iii) a consistent reduction in the numbers of splenic large CD5+ B cells and an oscillatory increase in the number of cells with CD5- phenotype; (iv) a late reduction in the numbers of splenic total CD5+ B cells. These results are consistent with the notion that thalidomide controls a disease-associated expansion of B cells in autoimmune prone mouse strains through a stimulatory effect of the drug on the immune system.

Animals↗
PubMed1994

In vitro characteristics of 'undercollected' units of whole blood in CP2D-A.

Blood donation volumes less than 350 ml are classified as 'undercollected' at the NSW Red Cross Blood Transfusion Service (BTS) and are discarded. This study evaluated the in vitro characteristics during storage of both undercollected units and units of acceptable volume. Thirty-two units of whole blood were each collected into 63 ml of CP2D-A, with blood volumes ranging from 180 to 456 ml. The units were stored between 4 and 6 degrees C for 35 days and in vitro measurements were performed weekly. Biochemical parameters measured included ATP, extracellular pH, total haemoglobin, haematocrit, mean cell volume, plasma sodium and potassium, plasma haemoglobin, 2,3-DPG and lactate levels. All parameters were within the BTS acceptable quality control limits for whole blood. Thus, it appears feasible to transfuse undercollected units with volumes between 180 and 350 ml. However, routine transfusion of undercollected homologous units is undesirable. In contrast, it may be preferable to transfuse an autologous unit, even if it was undercollected. The performance of in vivo survival studies would provide confirmatory data on this proposition.

2,3-Diphosphoglycerate↗
PubMed1994

Mitral mechanical valve without long-term anticoagulation. Eight-year follow-up.

In 12 patients with sinus rhythm (including 5 children and 6 young women), mitral valve replacement was performed with a microporous-surfaced valve similar to the Björk-Shiley Monostrut. After the first 3 months, permitting endothelialization of the suture ring to continue over the groove and adjacent metal valve ring, no long-term anticoagulant treatment was given. There was no thromboembolic complication in this group during follow-up for 6-8 years, during which four women gave birth to a total of seven children. In eight other cases, one mitral case with atrial fibrillation, anti-coagulant was not discontinued, and in the remaining aortic cases it was reinstituted. One of them (with atrial fibrillation) had hematuria during inadequate anticoagulant medication, but no thromboembolism. Of five patients with only aortic valve replacement, two had thromboembolic complications, one without residual symptoms and one with slight hand weakness. Another had a transient ischemic attack while on anticoagulant and acetylsalicylic acid was added. Two patients with aortic and mitral valve replacement died, one from heart tamponade and the other from venous thrombosis with pulmonary embolism.

Adolescent↗
PubMed1993

Changes in left ventricular diameter during intravenous induction of anesthesia.

Transthoracic two-dimensional echocardiography was used to measure left ventricular diameter in end-systole and end-diastole during anesthetic induction in 11 patients before coronary artery bypass grafting. Midazolam, 0.1 mg/kg, and fentanyl, 6 to 10 micrograms/kg, were used followed by pancuronium, 0.1 mg/kg. Lidocaine, 1.5 mg/kg, was given topically in the airways before intubation. During induction of anesthesia there was a gradual decrease in diastolic diameter (preload) and in systolic diameter and pressure (afterload). The decrease in end-diastolic diameter from 4.6 cm to 3.9 cm indicated a decrease in preload, defined as end-diastolic volume, by approximately 34%. These results are in agreement with earlier findings using calculated ventricular volumes, based on the determination of either ejection fraction with radionuclide cardiography or stroke volume with thermodilution, during induction of anesthesia with thiopental, diazepam, fentanyl, and pancuronium.

Aged↗
PubMed1993

Lipid synthesis and apolipoprotein gene expression in hepatocytes in primary culture from (puromycin-induced) nephrotic rats.

Primary culture of hepatocytes from puromycin aminonucleoside-induced nephrotic rats were used to discriminate between the hepatic and extra-hepatic contribution to the hyperlipidemia occurring in the nephrotic syndrome. De novo lipogenesis and utilization of exogenous fatty acids were not modified in nephrotic hepatocytes as compared to controls. In contrast 2.2 and 5.3-fold more triacylglycerol and phospholipids were secreted respectively by nephrotic hepatocytes than by controls. Triacylglycerol overproduction was not associated with an increase either in apo B mRNA level or in apo B synthesis or secretion measured by [35S]-methionine incorporation and immunoprecipitation. We also observed a significant increase in apo AI and apo E synthesis and secretion by nephrotic hepatocytes. This increase was correlated with a greater amount of apo AI and apo E mRNA than in controls. The overproduction of apo AI and apo E by nephrotic hepatocytes might intervene in the clearance of plasma lipoproteins and the redistribution of plasma cholesterol.

Albumins↗
PubMed1992

Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored at 22 degrees C.

Platelets stored in CLX blood bags, under normal blood banking conditions, were studied for up to 7 days to determine if changes occurred in the levels of membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal antibodies (MAB) were used to estimate the number of glycoprotein molecules on the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained essentially unaltered during storage. In contrast, the content of GP Ib at day 7 decreased by 45% of the total when fresh. The aggregation response to ristocetin, which requires GP Ib, was also diminished after 7 days. Addition of protease inhibitors, leupeptin and/or aprotinin did not appear to influence the degradation of this glycoprotein. We conclude that storage at 22 degrees C had deleterious effects on the GP Ib content of platelets.

Antibodies, Monoclonal↗
PubMed1992

Protective effect of a T-cell-dependent immunosuppressive, B-cell-mitogenic protein (F3'EP-Si, or P90) produced by Streptococcus intermedius.

The role of a previously described bacterial protein (F3'EP-Si), now designated P90, in the survival of Streptococcus intermedius in the host was investigated, and the immunosuppressive and B-cell-mitogenic effects of this protein were further characterized. C57BL6 mice treated with P90 were about 50 times more susceptible to infection with this bacterium than untreated mice. One of seven splenocytes of C57BL/6 mice were activated by P90. Marked splenomegaly was observed in mice treated with P90, with increased numbers of splenic mononuclear cells and polyclonal immunoglobulin-secreting plaque-forming cells. Peak responses were seen on day 3 for immunoglobulin M (IgM) and on day 5 for IgG, with an isotypic pattern consisting predominantly of IgG2a and IgG2b. When mice were treated with P90 before being primed with sheep erythrocytes, polyclonal immunoglobulin synthesis was accompanied by an ephemeral stimulation of the specific immune response against sheep erythrocytes that was quickly replaced by a dramatic immunosuppression. In contrast, when mice were treated with P90 after being primed, the polyclonal activation was comparatively much less evident and there was no suppression of the specific immune response. Immunosuppression was considerably reduced in mice thymectomized as adults or depleted of CD8+ cells. Adoptive transfer experiments showed that B cells obtained from P90-treated mice were less able to respond to an antigenic challenge, even in the presence of normal T cells, and that T cells obtained from P90-treated mice could actively suppress the specific immune response of normal B cells.

Animals↗
PubMed1992

Evidence of drainage of tungsten particles introduced in the pleural space through the visceral pleura into the lung parenchyma.

Studies of pleural clearance of calcium tungstate particles were made in the dog. By using scanning electron microscopy and elemental microanalysis, we show that mesothelial cells of the visceral leaflet of the pleura are also involved in the clearance of particles present in the pleural space. The histological study of lung parenchyma shows many macrophages loaded with tungsten particles, and we conclude that this way may be an important pathway for the transmission of pathologic processes from the pleural space to the lung.

Absorption↗
PubMed1992

[Nutritional regulation of apolipoprotein genes. Effect of dietary carbohydrates and fatty acids].

The effect of nutritional factors on apolipoprotein gene expression by rat liver were studied. Dietary carbohydrates or fatty acids regulate the expression of apo E gene, by altering either gene transcription or mRNA stability. Conversely, apo A1 regulation occurs at a post transcriptional level. In vivo and in vitro experiments gave contradictory results concerning apo B gene expression. The more dramatic changes in plasma lipids and apolipoproteins are obtained under dietary fish oil. Hepatocytes from fish oil-fed rats retain for several days modification in fatty acid metabolism, i.e. a shift in oleic acid channeling towards oxidation at the expense of esterification and a reduced ability to synthesize and secrete triacylglycerol. These modifications are paralleled with a decrease in the synthesis and in the secretion of apo Bs. Hepatocytes from fish oil fed rats secrete degradative forms of apo B which might result from either a sluggish VLDL synthesis and secretion or a more specific effect of n-3 long chain polyunsaturated fatty acid peroxidative products. Hepatocytes from fish oil fed rats exhibit a reduced ability to synthesize cholesterol, associated with a decrease in apo A1 synthesis and secretion without any modification in apo A1 mRNA. In contrast, the hepatocytes exhibit a concomitent decrease in apo E synthesis and secretion and in cellular apo E mRNA levels.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Effect of simvastatin on the synthesis and secretion of lipoproteins in relation to the metabolism of cholesterol in cultured hepatocytes.

In primary culture of rat hepatocytes, simvastatin, a powerful HMGCoA reductase inhibitor, inhibited acetate incorporation into cellular and secreted cholesterol and cholesteryl-esters, without any significant effect on triacylglycerol synthesis and secretion. When applied to the culture for 24 h at 10(-7) M, a concentration shown to inhibit cholesterol synthesis by 61%, simvastatin increased apolipoprotein BH and BL synthesis and secretion and strongly decreased apolipoprotein AI synthesis and secretion whereas apolipoprotein AIV remained unaffected. The synthesis and secretion of apolipoprotein E was only slightly affected in contrast with other situations where cholesterol synthesis decreased. All of these modifications occurred at a post-transcriptional level, as the corresponding messenger RNAs of the apolipoproteins did not vary. These results suggest that either the drug itself or variations in cholesterol synthesis might be involved in apo B and apo AI synthesis and secretion.

Animals↗
PubMed1991

Distinguishing mammalian sialidases by inhibition kinetics with novel derivatives of 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonic acid, an unsaturated derivative of N-acetylneuraminic acid.

Kinetic analysis of mammalian sialidases was carried out using analogs of the potent sialidase inhibitor, 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonic+ ++ acid (1). Substitutents at C-9 in place of the terminal hydroxyl group included a, 4-azido-2-nitrophenylthio group to give 5-acetamido-2,6-anhydro-9-S-(4-azido-2-nitrophenyl)-3,5, 9-trideoxy-9-thio-D-glycero-D-galacto-non-2-enonic acid (2), and an azide group to give 5-acetamido-2,6-anhydro-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-non-2 -enonic acid (3). Competitive inhibition kinetics were observed when 1,2, and 3 were tested with the lysosomal sialidase (cultured fibroblasts) and the plasma membrane sialidase (adenovirus DNA-transformed, human embryonic kidney cells), giving a Ki of about 10 microM for both enzymes with all three compounds. In contrast, only 1 was a potent inhibitor of the microsomal sialidase (rat muscle).

Adenoviridae↗
PubMed1991

Effect of dietary fish oil and corn oil on lipid metabolism and apolipoprotein gene expression by rat liver.

A 3-week fish oil diet induced in weanling rats a decrease in plasma lipids and liver triacylglycerol, and an increase in insulinemia, compared to a corn oil diet. At the same time, plasma apolipoprotein (apo) A-I was slightly lower and plasma heavy apo B/light apo B ratio was higher in fish-oil-fed than in corn-oil-fed rats. Hepatocytes obtained from fish-oil-fed and corn-oil-fed rats were used to examine how fish oil affects lipid and apolipoprotein synthesis and secretion. Primary culture of hepatocytes from fish-oil-fed rats displayed a lower ability to synthesize and secrete triacylglycerol than hepatocytes from corn-fed rats, as measured by mass determination or [U-14C]glycerol incorporation. Hepatocytes from fish-oil-fed rats exhibited a lower synthesis of cholesterol, measured by [14C]acetate incorporation, than hepatocytes from corn-oil-fed rats. This impairment was associated with an increase in beta-oxidation, a higher channeling of oleic acid into phospholipids, and a lower triacylglycerol/diacylglycerol ratio in hepatocytes from fish-oil-fed rats than in hepatocytes from corn-oil-fed rats. Incorporation of [35S]methionine into secreted apoB was reduced in hepatocytes from fish-oil-fed rats, but was not paralleled by a decrease in apo B mRNA. The appearance of degradative forms of apo B suggest an increase in apo B degradation in hepatocytes from fish-oil-fed rats. Incorporation of [35S]methionine into cellular and secreted apo A-I was lower in hepatocytes from fish-oil-fed rats than in hepatocytes from corn-oil-fed rats, and was not paralleled by any difference in the apo A-I mRNA level. Finally, [35S]methionine incorporation into cellular and secreted forms of apo E and apo A-I mRNA were reduced in hepatocytes from fish-oil-fed rats, compared with hepatocytes from corn-oil-fed rats. These combined data show that fish oil diet reduces triacylglycerol synthesis and secretion and affects apo B synthesis at a post-transcriptional level, and reduces cholesterol synthesis and affects apo E and apo A-I synthesis at a transcriptional and a post-transcriptional level.

Animals↗
PubMed1991

Nutritional regulation of apolipoprotein genes: effect of dietary carbohydrates and fatty acids.

The effect of nutritional factors on apolipoprotein gene expression by rat liver were studied. Dietary carbohydrates or fatty acids regulate the expression of apo E gene, by altering either gene transcription or mRNA stability. Conversely, apo AI regulation occurs at a post transcriptional level. In vivo and in vitro experiments gave contradictory results concerning apo B gene expression. The more dramatic changes in plasma lipids and apolipoproteins are obtained under dietary fish oil. Hepatocytes from fish oil-fed rats retain for several days modification in fatty acid metabolism, i.e. a shift in oleic acid channeling towards oxidation at the expense of esterification and a reduced ability to synthesize and secrete triacylglycerol. These modifications are paralleled with a decrease in the synthesis and in the secretion of apo Bs. Hepatocytes from fish oil fed rats secrete degradative forms of apo B which might result from either a sluggish VLDL synthesis and secretion or a more specific effect of n-3 long chain polyunsaturated fatty acid peroxidative products. Hepatocytes from fish oil fed rats exhibit a reduced ability to synthesize cholesterol, associated with a decrease in apo AI synthesis and secretion without any modification in apo AI mRNA. In contrast, the hepatocytes exhibit a concomitent decrease in apo E synthesis and secretion and in cellular apo E mRNA levels.

Animals↗
PubMed1991

The interaction of pseudohalides with the phospholipid head-group: a nuclear magnetic resonance study.

Liposomes have been studied by means of high-field magnetic resonance techniques. The choline N+(CH3)3 group showed two proton resonances for phosphatidylcholine whereas the addition of a charged species to the phospholipid resulted in a single N+(CH3)3 resonance. Upon the addition of either of two linear pseudohalide anions, the two resonances for phosphatidylcholine were further split whereas for the mixture of lipids containing a charged species, the single head-group resonance was now split. The presence of a negative charge on the liposome does not prevent the anion-liposome interaction observed for neutral liposomes. Incorporation of cholesterol into the negatively charged liposomes results in a clear initial splitting of the head-group proton signal in a manner very similar to that for neutral liposomes; this head-group signal is then further split upon anion addition. The small splitting involved suggests a weak pseudohalide-liposome interaction whose magnitude depends on the position of the anion in the lyotropic series. The phosphorous NMR signal from the head-group is unaffected by the pseudohalide interaction whereas the carbon signals from the N+(CH3)3 groups are affected, indicating that the initial anion interaction is localized to the region of the choline groups of the liposome. After the initial exposure of the liposome to the anion, however, the splitting decreases with time, indicating that the anions have entered the liposome and interact with both inside and outside head-groups.

Carbon Isotopes↗
PubMed1990

Partial apolipoprotein E-beta-galactosidase fusion protein expressed in Escherichia coli retains binding activity to the LDL(B/E) receptor.

A partial rat apo E-beta-galactosidase fusion protein was produced in Escherichia coli Y1089 infected with recombinant lambda GT11 obtained by immunoscreening of a rat liver cDNA library with an anti-rat LDL antiserum. Partial cDNA overlapped the apo E mRNA sequence coding for apo E binding domain towards the LDL(B/E) receptor up to codon for Arg-139. Fusion protein specifically bound to human fibroblasts. The high-affinity component exhibited a Kd of 5 x 10(-8) M and 4.1 x 10(5) sites per cell. Fusion protein binding to fibroblasts was mediated by their apo E moiety and not by beta-galactosidase since: (1) specific binding of fusion protein was competed out by human LDL; (2) beta-galactosidase did not compete with fusion protein binding; and (3) human fibroblasts from a patient with familial hypercholesterolemia, deficient in LDL(B/E) receptor, bound fusion protein 10-times lower than control fibroblasts. It was demonstrated that partial fusion protein retained the functional activity of the native apo E. However, compared to full-length native or engineered apo E, fusion protein was able to bind fibroblasts without being complexed with phospholipids. Fusion proteins might be a useful tool for studying the functional efficiency of the LDL(B/E) receptor and for mapping residues and domains involved in the binding process.

Apolipoproteins E↗
PubMed1990

Amiodarone-liposome interaction: a multinuclear NMR and X-ray diffraction study.

Amiodarone, a potent antiarrhythmic drug, is widely used in cardiology. Its electrophysiological effects, as well as many of its side effects, seem to involve lipids. We report here a multinuclear NMR and X-ray diffraction study of amiodarone in egg phosphatidylcholine liposomes and lipid multilayers. In proton NMR experiments, amiodarone alters the signal from the lipid trimethyl ammonium group for pH values ranging from 3.2 to 8.4; cholesterol does not cause this alteration. The addition of SCN- changes both the proton and phosphorus NMR spectra of liposomes containing amiodarone. For both proton and carbon NMR, amiodarone modifies the signal from the lipid methylene groups, but to a far lesser extent than does cholesterol. Incorporation of amiodarone in EPC bilayers also modifies the low-angle X-ray diffraction patterns, decreasing the lamellar repeat period at low water contents, but swelling the fluid spaces between bilayers at high water contents. Electron density profiles and modeling studies using the X-ray data indicate that amiodarone decreases the bilayer thickness and adds electron density at the interfacial region of the bilayer. Our analysis of the NMR and X-ray data indicates that the iodine atoms of amiodarone are located near the hydrocarbon/water interface and that the tertiary amine of amiodarone is in the headgroup region of the bilayer.

Amiodarone↗