Surgical extracardiac thoracic complications in heart transplantation.
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Adult↗
Biomedical subjects
A Miralles
Publications and source records attributed to A Miralles.
Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, triflusal, and its deacetylated metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid.
The therapeutic potential of drugs that block the induction of cyclooxygenase-2 has been emphasized. When two 4-trifluoromethyl salicylate derivatives [2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and its deacetylated metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB)] were compared with aspirin and sodium salicylate as cyclooxygenase-2 (COX-2) inhibitors, we observed that in bacterial lipopolysaccharide-activated human blood, triflusal, aspirin, and HTB, but not sodium salicylate, inhibited COX-2-mediated prostaglandin E2 (PGE2) production (IC50 = 0.16, 0.18, 0.39, and >10 mM, respectively). However, only triflusal and aspirin inhibited purified COX-2 enzyme. To test this apparent discrepancy, we realized that HTB and triflusal (but neither aspirin nor salicylate) produced a concentration-dependent inhibition of COX-2 protein expression in peripheral human mononuclear cells. This observation was further confirmed in a rat air pouch model in vivo, in which both aspirin and triflusal inhibited PGE2 production (ID50 = 18.9 and 11.4 mg/kg p.o., respectively) but only triflusal-treated animals showed a decrease in COX-2 expression. This different behavior may be, at least in part, due to the ability of HTB and triflusal to block the activation of the transcription factor nuclear factor-kappaB to a higher extent than aspirin and sodium salicylate. Thus, in addition to inhibiting the COX-2 activity at therapeutic concentrations, triflusal is able to block through its metabolite HTB the expression of new enzyme, and hence the resumption of PGE2 synthesis. Triflusal and HTB may exert beneficial effects in processes in which de novo COX-2 expression is involved and, in a broader sense, in pathological situations in which genes under nuclear factor-kappaB control are up-regulated.
Animals↗
[Atypical primary biliary cirrhosis or autoimmune cholangitis?].
The term autoimmune cholangitis is used for a disease with clinical and pathological features of primary biliary cirrhosis (PBC), lack of anti-mitochondrial antibodies (AMA), presence of anti-nuclear antibodies (ANA), and good response to immunosuppresive therapy. The current knowledge of this condition is limited and it is not established whether or not it is a different syndrome from the CBP. We report a 51-year-old woman with chronic cholestasis, histological features of PBC, negative AMA and positive peripheral fluorescent ANA pattern, without response to prednisone.
Antibodies, Antinuclear↗
Effects of the alkylating agent EEDQ on regulatory G proteins and recovery of agonist and antagonist alpha2-adrenoceptor binding sites in rat brain.
The aim of this study was to assess the effect of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced alpha2-adrenoceptor inactivation on regulatory G proteins and the recovery of agonist and antagonist binding sites. EEDQ induced a rapid increase in the abundance of rat brain cortical Galphai1/2 proteins (30% at 6 h) which reached a maximum at 4 days (45%) and which then slowly returned (7-30 days) to control values. EEDQ did not alter significantly the levels of Galphai3 and Galphao proteins. By using the standard monoexponential model, the analysis of the recovery of alpha2-adrenoceptor density (6 h-30 days) with [3H]UK 14304 (bromoxidine) and [3H]RX 821002 (2-metoxy idazoxan) in the cerebral cortex did not reveal differences in receptor turnover parameters. However, the recovery of [3H]UK 14304 binding fitted best to a new biphasic recovery model, suggesting the existence of two distinct phases of recovery of agonist sites (r1 and r2 = 15.7 and 7.4 fmol mg protein(-1) day(-1); k1 and k2 = 0.51 and 0.25 day(-1); (t1/2)1 and (t1/2)2 = 1.4 and 2.7 days). In contrast, the recovery of [3H]RX 821002 antagonist sites did not fit to the biphasic model (r = 8.1, k = 0.14, t1/2 = 4.9). Because agonist binding requires coupling to G proteins, the present results suggest that the rapid over-expression of Galphai1/2 proteins induced by EEDQ is related to the biphasic recovery of [3H]UK 14304 binding. The possible implication of the faster recovery of alpha2-adrenoceptor function after EEDQ inactivation is discussed.
Adrenergic alpha-2 Receptor Agonists↗
Characterization of platyhelminth POU domain genes: ubiquitous and specific anterior nerve cell expression of different epitopes of GtPOU-1.
POU domain proteins are a large family of transcription factors that have been identified in a variety of metazoans, from freshwater sponges, planarians and nematodes to arthropods, echinoderms and vertebrates. Many of these proteins are implicated in the development and establishment of the nervous system. In this paper we describe the identification of the planarian genes GtPOU-1, GtPOU-3 and GtPOU-4, which belong to the subclasses III and IV of POU-domain genes. Their similarity with other members of the POU family is restricted to the POU and homeo domains, plus some peptide sequences scattered in the linker and flanking regions. As with other subclass III POU genes, GtPOU-1 is devoid of introns. Axial transcript distribution by RT-PCR and immunohistochemical assays, performed with a polyclonal antibody raised against the GtPOU-1 fusion protein, indicate that both the GtPOU-1 transcript and protein are continuously expressed along the antero-posterior axis. A monoclonal antibody raised against the same fusion protein indicates that a GtPOU-1-specific epitope, probably obtained by post-translational modification, is present in neural cells from both the central and peripheral nerve systems of the adult planarian's anterior third. Moreover, the GtPOU-1-specific epitope shows a dynamic expression pattern during regeneration, always marking the most anterior region of the planarian nervous system. Both the rapid and general GtPOU-1-specific epitope modification, during posterior regeneration, indicate that regeneration is a global process involving all planarian regions, including those that are far from the wound, by a combination of morphallactic and epimorphic mechanisms.
Amino Acid Sequence↗
Isolation of two CD50 (ICAM-3)-negative Jurkat T-cell clones and their application for analysis of CD50 function.
The leukocyte differentiation antigen CD50 (intercellular adhesion molecule-3, ICAM-3), mediates cell-cell adhesion through its ligand LFA-1 and is a transducting receptor molecule during T-cell activation. Since CD50 homologues in other species have not yet been identified, the role of this molecule can only be analyzed in human cell models. Thus, to better study CD50 function in T cells, we have obtained two CD50-negative T-cell clones, named CAMY.1 and CAMY.2. These clones were derived from the Jurkat T-cell variant PPL.1. Data from analysis of protein expression, specific mRNA content and calcium mobilization assays have confirmed the absence of functional CD50 molecules on these two clones. Thus, CAMY.1 and CAMY.2 show no CD50 expression by phenotypical and immunoprecipitation analysis. CD50-specific mRNA content is undetectable by Northern blot analysis in these clones and, only, when RT-PCR was performed could specific mRNA be detected. Additionally, CD50 cross-linking on theses clones shows no increase in intracellular calcium. Transfection of CD50 cDNA on CAMY cells restores not only CD50 surface expression, but its functional ability to induce calcium mobilization, CD69 upregulation and cell morphological changes. The CAMY.1 and CAMY.2 clones provide useful model systems to analyze CD50 function in T cells.
Animals↗
[Aneurysms of the left ventricle. Surgical treatment].
Left ventricular aneurysm as a complication of myocardial infarction is observed in 10% of patients. In recent years, all surgical teams have observed a significant decrease of this complication. There is no doubt that this is due to the current medical treatment in the acute phase of myocardial infarction. Surgical treatment is considered only when the ventricular aneurysm presents complications such as congestive heart failure, thromboembolism, malignant ventricular arrhythmias or angina. In this review, we comment on the principle surgical procedures reported up to now. The indication of surgery is based on good functional results and long-term survival.
Heart Aneurysm↗
Role of lipid polymorphism in G protein-membrane interactions: nonlamellar-prone phospholipids and peripheral protein binding to membranes.
Heterotrimeric G proteins (peripheral proteins) conduct signals from membrane receptors (integral proteins) to regulatory proteins localized to various cellular compartments. They are in excess over any G protein-coupled receptor type on the cell membrane, which is necessary for signal amplification. These facts account for the large number of G protein molecules bound to membrane lipids. Thus, the protein-lipid interactions are crucial for their cellular localization, and consequently for signal transduction. In this work, the binding of G protein subunits to model membranes (liposomes), formed with defined membrane lipids, has been studied. It is shown that although G protein alpha-subunits were able to bind to lipid bilayers, the presence of nonlamellar-prone phospholipids (phosphatidylethanolamines) enhanced their binding to model membranes. This mechanism also appears to be used by other (structurally and functionally unrelated) peripheral proteins, such as protein kinase C and the insect protein apolipophorin III, indicating that it could constitute a general mode of protein-lipid interactions, relevant in the activity and translocation of some peripheral (amphitropic) proteins from soluble to particulate compartments. Other factors, such as the presence of cholesterol or the vesicle surface charge, also modulated the binding of the G protein subunits to lipid bilayers. Conversely, the binding of G protein-coupled receptor kinase 2 and the G protein beta-subunit to liposomes was not increased by hexagonally prone lipids. Their distinct interactions with membrane lipids may, in part, explain the different cellular localizations of all of these proteins during the signaling process.
Animals↗
Aortic mismatch in heart transplantation: readaptation.
Great vessel mismatch between donor and recipient is very usual in heart transplantation. Different procedures have been used to manage this situation. A tailoring aortoplasty is described, as a technical alternative, in cases of considerable size incongruence between donor and recipient aortic diameters.
Adolescent↗
Hyperinsulinemia as a determinant of microalbuminuria in essential hypertension.
OBJECTIVE: To analyze the relationship between insulinemia and urinary albumin excretion in a group of nonobese, young adult hypertensive patients, who had never been treated with antihypertensive drugs. PATIENTS AND METHODS: Forty-nine patients who fulfilled the inclusion criteria were included. Twenty-four-hour ambulatory blood pressure monitorings, urinary albumin excretion (UAE) measurements, and an oral glucose-tolerance test measuring glucose and insulin, were performed, and left ventricular mass was measured by echocardiography. Hypertensive patients were classified as normoalbuminuric when their UAE was < 30 mg/24 h (40 patients; mean UAE 13.4 +/- 7.0 mg/24 h), and as microalbuminuric when their UAE was 30-300 mg/24 h (nine patients; mean UAE 90.5 +/- 86.6 mg/24 h). RESULTS: In comparison with that of the normoalbuminuric group, the fasting plasma glucose concentration for the microalbuminuric group was only slightly higher (100 +/- 9 versus 95 +/- 8 mg/dl, NS). In contrast, the fasting insulin concentration in the microalbuminuric group was significantly higher than that observed in the normoalbuminuric group (25.2 +/- 6.7 versus 16.6 +/- 5.2 microU/ml, P<0.0001). During the oral glucose-tolerance test, the area under the curve (AUC) for glucose (317 +/- 41 versus 253 +/- 53 mg/dl x 2/h, P<0.001) and the AUC for insulin (253 +/- 171 versus 124 +/- 43 microU/ml x 2/h, P<0.001) were significantly higher in the microalbuminuric group than were those AUC observed in the normoalbuminuric group. After adjustments for age, sex, body mass index and average 24 h ambulatory mean blood pressure were made, the fasting insulin level was associated independently with an increase in UAE in a multiple regression model with base 10 logarithm of the UAE as the dependent variable. Variations in fasting insulin level alone accounted for 33% of the UAE variance. In contrast, the 24 h ambulatory mean blood pressure, rather than the insulin level, was the strongest predictor of the left ventricular mass index. CONCLUSIONS: Mild hypertensive patients with microalbuminuria were hyperinsulinemic in the absence of obesity, and their insulin level was the main determinant of microalbuminuria in these patients. Microalbuminuria in essential hypertension seems to identify patients with a cluster of cardiovascular risk factors and a bad risk profile. Thus, assessment of microalbuminuria may be useful in the stratification of risk in essential hypertension.
Adult↗
Surgical treatment of Brucella endocarditis.
Between April 1987 and October 1992, six cases of Brucella endocarditis were operated on in the authors' hospital for valve replacement. They were five men and one woman with a mean(s.d.) age of 52(15) years (range 30-71 years). Three patients were in New York Heart Association (NYHA) class III and three in class IV. Two patients had previous history of rheumatic fever, one was a drug abuser, two had peripheral embolism and one constrictive pericarditis. Most were living in rural areas. Echocardiographic diagnoses were: severe aortic regurgitation in two patients, mixed disease in two and double valve involvement in two. Valve vegetations were demonstrated in two patients, valve calcification in two and annulus abscess in two others. Serological tests were positive in all patients. All patients had valve replacements and three were operated on as emergencies. Surgical findings were: valve vegetations in two patients, cusp perforation in two annulus abscess in two and prosthetic leak in two. Mean(s.d.) cardiopulmonary bypass time was 123(77) min with a mean ischaemic time of 79(43) min. All patients were given specific antibiotic treatment after surgery. There was no intraoperative mortality and the 5-year survival rate was 100%. Early reoperations were needed in three patients, two because of prosthetic leakage causing severe regurgitation and one for tamponade. The results suggests that Brucella endocarditis is rare, but still occurs in Mediterranean areas. Surgical replacement is needed in spite of antibiotic treatment and recurrences with prosthetic leaks are usual.
Adult↗
Early graft failure after heart transplantation due to coronary artery embolization with myocardial tissue.
Myocardial infarction due to myocardial tissue embolism of the right coronary is a rare cause of early graft failure. We report one case with such a complication, in a 44-year-old man who was transplanted with a graft from a 32-year-old male donor. Prolonged refractory cardiogenic shock developed after orthotopic heart transplantation. A right coronary artery bypass graft was performed and the patient was supported with a biventricular assist device for 69 h. Despite that, no improvement of the graft contractility was observed and the patient could not recover from shock. Pathologic examination showed inferior and septal acute infarction. An embolus of myocardial tissue was completely occluding the first portion of the right coronary artery. The tissue probably came from suture lines of the left atrium.
Adult↗
Expression of intercellular adhesion molecule-3 (ICAM-3/CD50) in malignant lymphoproliferative disorders and solid tumors.
ICAM-3/CD50 is a recently described LFA-1 counter receptor that seems to play an important role in the initiation of immune responses. In this study we have examined the expression of ICAM-3/CD50 in a large series of human neoplasms including 101 Non-Hodgkin's lymphomas (NHL), 26 Hodgkin's disease, and 38 solid tumors to define the distribution patterns of this molecule in malignant neoplasms and their possible correlation with clinical and pathological characteristics of the patients. In NHL, ICAM-3/CD50 was expressed in almost all the tumors with a tendency to be lost in high grade lymphomas. Reed-Sternberg cells and their variants in Hodgkin's disease were always negative independently of the histological subtype of the disease. No expression was observed in tumor epithelial cells of the 38 solid tumors examined. Strong endothelial cell staining was observed in 31% of the NHL and 31% of Hodgkin's disease. ICAM-3 expression in these cases was restricted to small tumor vessels. ICAM-3 expression in endothelial cells of NHL was significantly more frequent in high grade (40%) than in low grade lymphomas (14%) (p = 0.012). In addition, tumor vessels were also positive in 29% of solid tumors independently of the histological type. No correlation was observed between ICAM-3 expression in tumor or endothelial cells and other clinical and pathological characteristics of the patients. These findings indicate that ICAM-3 expression in human tumors is restricted to hematological neoplasms with a tendency to be lost in high grade lymphomas and Hodgkin's disease. ICAM-3 is also expressed by endothelial cells from tumor-associated neovascularization in both lymphoid and solid tumors.
Animals↗
Microalbuminuria, left ventricular mass and ambulatory blood pressure in essential hypertension.
The objective of the present study was to assess the relationship between microalbuminuria (Malb) and left ventricular hypertrophy (LVH), when levels of ambulatory BP was token in to account as a confounder factor. Patients with essential hypertension, aged 25 to 50 years old, never treated with antihypertensive drugs, were included in the study. The inclusion criteria were: (a) absence of diabetes, renal disease or urinary tract infection; (b) urinary albumin excretion (UAE) estimated in urine of 24 hours in two separate days; (c) echocardiography suitable for measurement of left ventricular mass (LVM); and (d) good quality ambulatory blood pressure monitoring during 24 hours. UAE was measured using a immunonephelometric assay (Behring Institute) and Malb was considered when UAE 30 to 300 mg/24 hours during the two days. LVM was calculated by the Devereaux formula and referred to height (LVMI g/m). AMBP was performed using an oscilometric device (Spacelabs 90202 or 90207) during a regular working day. Readings were programmed every 20 minutes between 6 a.m. to midnight and thereafter every 30 minutes. The average BP during a 24 hour period was calculated. One hundred and fifty one patients (96 male, mean age 37 +/- 8 years, body mass index 27.7 +/- 3.7 g/m2) were included. The average values of office BP was 148 +/- 15/96 +/- 8 mm Hg, and the average BP during 24 hours was 137 +/- 13/88 +/- 12 mm Hg. UAE was 30.1 +/- 52.3 mg/24 hr and the LVMI 140.6 +/- 44.1 g/m. The percentage of Malb patients was 28% and those with LVH 34%. A significant relationship between UAE and office and ambulatory SBP and DBP was observed. LVMI was also significantly related to ambulatory SBP and DBP, a relationship that was not found for office BP. In a multiple regression model, significant relationship between UAE and LVMI emerged, independent of diastolic ambulatory BP, age and sex (P < 0.04). In conclusion; we observed a significant relationship between UAE and LVMI, in part, independent of blood pressure. The fact that Malb is associated with the presence of LVH, supports the idea that Malb is a risk marker in essential hypertensive patients.
Adult↗
Mobilization of peripheral blood progenitor cells by cyclophosphamide and rhGM-CSF in multiple myeloma.
Fifteen consecutive patients with multiple myeloma (MM) scheduled for peripheral blood progenitor cell (PBPC) transplantation, were randomly selected to receive cyclophosphamide (CY) (4 g/m2) alone (group I) or associated with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (5 micrograms/kg/day) (group II). The mean time of neutropenia after CY administration was 9.8 +/- 4.3 days in group I and 6.4 +/- 1.2 days in group II (P = 0.0228). One hundred and eight aphereses were performed (7.1 +/- 1.8 aphereses per patient in group I and 6.4 +/- 2.8 aphereses per patient in group II). rhGM-CSF administration after CY allowed a higher collection of CD34+ cells in apheresis products (1.42 +/- 1.68 x 10(6) CD34+ cells/kg) in comparison to without factor administration (0.47 +/- 0.52 x 10(6) CD34+ cells/kg) (P = 0.0165). The mean number of cells infused per patient was 6.56 +/- 4.02 x 10(8) MNC/kg and 7.64 +/- 3.00 x 10(4) CFU-GM/kg in group I and 6.25 +/- 4.03 x 10(8) MNC/kg and 8.16 +/- 9.73 x 10(4) CFU-GM/kg in group II. The mean time to recover 0.5 x 10(9) granulocytes/I, 20 and 50 x 10(9) platelets/I in peripheral blood (PB) was 17.2 +/- 7.4, 13.4 +/- 3.7 and 16.5 +/- 6.9 days respectively, in group I and 13.3 +/- 1.7, 11.6 +/- 1.6 and 15 +/- 6.3 days, in group II. rhGM-CSF administration after CY treatment for PBPC mobilization in MM patients reduces the neutropenic period after CY and enhances apheresis CD34+ cell collection.
Adult↗
Purine enzyme profile in human colon-carcinoma cell lines and differential sensitivity to deoxycoformycin and 2'-deoxyadenosine in combination.
Different cell lines, 2 from human colon carcinoma (LoVo and HT29) and 1 from Chinese hamster ovary (CHO K-I), were examined to assess the effect of deoxycoformycin (dCF), an inhibitor of adenosine deaminase (ADA), and 2'-deoxyadenosine (dAdo) on their growth. When used alone, neither dCF or dAdo were cytotoxic for the 3 cell lines, while their combination caused inhibition of cell growth, with the following sensitivity: CHO K-I > LoVo > HT29. We studied the pattern of enzymatic activities involved in the metabolism of dAdo in the 3 cell lines. The phosphorylation of dAdo by adenosine kinase appears to play a central role in the toxicity of the deoxynucleoside in combination with dCF. In fact, CHO K-I cells, which are the most sensitive, possess the highest level of this enzyme. Moreover, the cytotoxic effect was almost completely reversed in the 3 cell lines when inhibitors of adenosine kinase, such as 5'-amino-5'-deoxyadenosine and iodotubercidine, were added to the culture medium together with dCF and dAdo. In addition, baby hamster kidney (BHK) adenosine-kinase-deficient (AK-) cells were highly resistant to this treatment. Uptake inhibition of dAdo using dipyridamole also caused reversal of the toxicity. The AMP and deoxyAMP dephosphorylating activities, much lower in the CHO K-I cells, also appear to play a central role in the toxicity of dAdo when adenosine deaminase is inhibited. However, our data suggest that other factors may modulate the toxic effect, such as S-adenosyl-homocysteine-hydrolase inhibition by dAdo at high concentrations.
Adenosine Kinase↗
Pharmacological and immunological characterization of solubilized 130-140- and 66-kD imidazoline receptors in the rat brain.
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Animals↗
I2-imidazoline receptors in the healthy and pathologic human brain.
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Adrenergic alpha-2 Receptor Antagonists↗