PubMed Health⌕ Search

Biomedical subjects

A Miralles

Publications and source records attributed to A Miralles.

At least 73 records · Page 4Linked to original sources
PubMed1993

Differential effect of cryopreservation on natural killer cell and lymphokine-activated killer cell activities.

The use of lymphokine-activated killer (LAK) cell therapy in delayed treatment requires the use of cryopreserved effector cells. The purpose of this study was to determine the optimal cryopreservation protocol for the maintenance of cytotoxic activity in mononuclear cells (MNCs). MNCs were cryopreserved with dimethyl sulfoxide or 1,2-propanediol before and after 3 days of culture with recombinant interleukin 2. The effects of cryopreservation on cell recovery, LAK cell and natural killer (NK) cell cytotoxic activities, and surface antigen markers were studied. Recovery of nonactivated MNCs was higher with 1,2-propanediol than with dimethyl sulfoxide (p < 0.05). Cytotoxic activities, measured with a 51Cr release assay, significantly decreased after thawing, on both activated cells (76.3%; range, 35.8-92.2%) and fresh cells (54.6%; range, 17.5-75.4%). A 6-day kinetic test was used to compare the cytotoxic activity of cryopreserved and fresh cells. The results showed different patterns for NK cells (cryopreserved cells had lower levels of activity than fresh cells) and LAK cells (cryopreserved cells had higher levels of activity than fresh cells). Phenotype changes of effector cells in culture, with and without cryopreservation, were monitored by flow cytometry using monoclonal antibodies. These results were compared with changes in the cytotoxicity of cells with and without cryopreservation. After thawing, there was a decrease in MNCs expressing CD14 and CD56. Recovery of the CD56 marker correlates with increased cytotoxic activity. Despite some loss of NK cell activity, it is concluded that MNCs may be successfully cryopreserved before their use in immunotherapeutic treatment.

CD4-CD8 Ratio↗
PubMed1993

Differential effects of the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on brain alpha 2-adrenoceptors and I2-imidazoline sites in vitro and in vivo.

The alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) is a peptide-coupling agent that is being used to inactivate irreversibly alpha 2-adrenoceptors and other receptors. The aim of the present study was to assess the in vitro and in vivo effects of EEDQ on the newly discovered brain I2-imidazoline sites, located mainly in mitochondria. Preincubation of rat cortical membranes with EEDQ (10(-8)-10(-5) M) markedly decreased (20-90%) the specific binding of the selective antagonist [3H]RX821002 to alpha 2-adrenoceptors without affecting that of [3H]idazoxan (in the presence of adrenaline) to I2-imidazoline sites. In EEDQ-pretreated membranes (10(-5) M, 30 min at 25 degrees C), the density of I2-imidazoline sites (Bmax = 80 +/- 4 fmol/mg of protein) was not different from that determined in untreated membranes in the presence of (10(-6) M (-)-adrenaline (Bmax = 83 +/- 4 fmol/mg of protein), and both densities were lower (24%, p < 0.05) than the total native density of [3H]idazoxan binding sites (Bmax = 107 +/- 6 fmol/mg of protein) (I2-imidazoline sites plus alpha 2-adrenoceptors). Treatment of rats with an optimal dose of EEDQ (1.6 mg/kg, i.p., for 2 h to 30 days) reduced maximally at 6 h (by 95 +/- 1%) the specific binding of [3H]-RX821002 to alpha 2-adrenoceptors, but also the binding of [3H]idazoxan to I2-imidazoline sites (by 44 +/- 5%). Pretreatment with yohimbine (10 mg/kg, i.p.) fully protected against EEDQ-induced alpha 2-adrenoceptor inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Chronic treatment with the monoamine oxidase inhibitors clorgyline and pargyline down-regulates non-adrenoceptor [3H]-idazoxan binding sites in the rat brain.

1. The binding of [3H]-idazoxan in the presence of 10(-6) M (-)-adrenaline was used to quantitate non-adrenoceptor idazoxan binding sites (NAIBS) in the rat brain after treatment with various psychotropic drugs. 2. Chronic treatment (14 days) with the monoamine oxidase (MAO) inhibitors clorgyline (0.3-10 mg kg-1, i.p.) and pargyline (10 mg kg-1, i.p.), but not with Ro 41-1049 (1 mg kg-1, i.p.), markedly decreased (30-50%) the density of NAIBS in the cerebral cortex without any apparent change in the affinity of the radioligand. 3. Acute (1 day) and/or chronic treatments (14 days) with other psychotropic drugs such as desipramine (3 mg kg-1, i.p.), cocaine (10 mg kg-1, i.p.), reserpine (0.12 mg kg-1, s.c.), haloperidol (1 mg kg-1, i.p.) and diazepam (10 mg kg-1, i.p.) did not alter the density of NAIBS in the cerebral cortex. 4. In vitro, the propargylamines clorgyline, pargyline and deprenyl displaced the binding of [3H]-idazoxan to NAIBS from two distinct sites, but only clorgyline displayed an apparent very high affinity for a relevant population of NAIBS (KiH = 40 pM; KiL = 10.6 microM). The structurally diverse MAO inhibitors Ro 16-6491 (selective for MAO-B) and Ro 41-1049 (selective for MAO-A), as well as the other psychotropic drugs (desipramine, cocaine, reserpine and haloperidol) displaced the binding of [3H]-idazoxan to NAIBS monophasically and with very low potencies. As expected, the MAO inhibitors clorgyline and Ro 41-1049 displaced the binding of [3H]-Ro 41-1049 to MAO-A monophasically and with high potencies (Ki values: 0.18 nM and 22 nM, respectively). In contrast, idazoxan displayed very low affinity (Ki =40 microM) against the binding of pH]-Ro 41-1049 to MAO-A. These results disprove a direct interaction between [3H]-idazoxan and the enzyme MAO.5. Preincubation of cortical membranes with clorgyline (10-9M or 10-6 M for 30 min) or pargyline(10-6 M or 10-5M for 30 min), reduced by 30-50% and by 17-30%, respectively, the total density of NAIBS without any apparent change in the affinity of the radioligand. Preincubation with 10-6M clorgyline did not alter the affinity of cirazoline for the two populations of NAIBS, but reduced by 60%the binding of [3H]-idazoxan to the high affinity site without affecting the binding of the radioligand to the low affinity site. These results indicate that the two MAO inhibitors irreversibly block the binding of[3H]-idazoxan to NAIBS.6. In vivo, however, various acute treatments with clorgyline (1-20 mg kg-1, i.p.) for different time intervals (6-48 h) did not alter the density of NAIBS. In vivo, only very high doses of clorgyline (40 and 80 mg kg-1, i.p.) induced modest decreases (21-28%) in the density of NAIBS in the cerebral cortex.7. Together the results indicate that the irreversible binding of clorgyline and pargyline to NAIBSfound in vitro does not fully explain the marked decreases in the density of NAIBS found in vivo after the chronic treatments. It is suggested that the down-regulation of NAIBS induced in vivo by clorgyline and pargyline, through a direct or indirect mechanism, may have functional implications.

Animals↗
PubMed1993

Acceleration by chronic treatment with clorgyline of the turnover of brain alpha 2-adrenoceptors in normotensive but not in spontaneously hypertensive rats.

1. The aim of this study was to quantitate and compare the turnover of alpha 2-adrenoceptors in the cerebral cortex of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, and its modulation during chronic treatment with the monoamine oxidase (MAO) inhibitor, clorgyline. 2. In SHR, the specific binding of the agonist [3H]-UK 14304 and of the antagonist [3H]-RX 821002 was significantly reduced in the brain (Bmax 15-19% lower) as compared to that in sex- and age-matched WKY rats. In contrast, no significant changes in the Kd values for both radioligands were found between WKY and SHR rats. Therefore, SHR rats offer a genetic model with a lower density of alpha 2-adrenoceptors in the brain. 3. Chronic treatment (21-35 days) with clorgyline (1 mg kg-1, i.p.) markedly decreased the density of brain alpha 2-adrenoceptors ([3H]-UK 14304 binding) in Sprague-Dawley (Bmax reduced by 50%) and in WKY (Bmax reduced by 30%) rats without any apparent change in the affinity of the radioligand. In contrast, the density of brain alpha 2-adrenoceptors in SHR was not down-regulated by chronic clorgyline treatment. 4. The recovery of [3H]-UK 14304 binding after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 1.6 mg kg-1) (an alkylating agent for the alpha 2-adrenoceptor) was assessed in control and clorgyline-treated (1 mg kg-1; i.p. for 7-21 days) WKY and SHR rats to study the process of alpha 2-adrenoceptor repopulation and to calculate receptor turnover parameters. 5. The simultaneous analysis of receptor recovery curves revealed that the turnover of brain alpha2-adrenoceptors in SHR rats was accelerated (k = 0.141 day-1;t 1/2= 4.9 days; r/k =40 fmol mg-1 protein)compared to that in WKY rats (k = 0.085 day-1; tl/2= 8.1 days; r/k = 54 fmol mg-1 protein) and that the reduced density of cortical alpha2-adrenoceptors (Bmax or r/k values) in SHR was probably due to an abnormal higher receptor degradation (delta k = 66%) and not to a decreased receptor synthesis which in fact showed a slight increase (delta r = 24%).6. Treatment with clorgyline (1 mg kg-1, i.p. for 21 days) accelerated the turnover of brain alpha2-adrenoceptors in WKY rats (k = 0.328 days-1; tl/2= 2.1 days; r/k = 29 fmol mg-1 protein) and the greater increase in receptor degradation (delta k = 286%) over receptor synthesis (delta r = 109%) led to down-regulation of receptor density (r/k = 46% lower). In contrast, treatment with clorgyline did not modify significantly the turnover of brain M2-adrenoceptors in SHR (k = 0.192 days-1; t1/2 = 3.6 days;r/k = 39 fmol mg-1 protein), indicating that in this genetic model of hypertension, the desensitized alpha2-adrenoceptors cannot be further down-regulated by clorgyline treatment and that they lack the expected adaptative increase in receptor synthesis.

Adrenergic alpha-Agonists↗
PubMed1993

Discrimination and pharmacological characterization of I2-imidazoline sites with [3H]idazoxan and alpha-2 adrenoceptors with [3H]RX821002 (2-methoxy idazoxan) in the human and rat brains.

The alpha-2 adrenoceptor antagonist idazoxan has been shown to also recognize with high affinity nonadrenoceptor sites (I2-imidazoline sites). In contrast, the 2-methoxy derivative of idazoxan, 2-methoxy idazoxan (RX821002), binds almost exclusively to alpha-2 adrenoceptors. The purpose of this study was to assess and extend the pharmacological characterization of I2-imidazoline sites and alpha-2 adrenoceptors in the human and rat brains. Competition studies with several imidazoli(di)ne/guanidine drugs and other nonrelated structures were performed in cortical membranes against [3H]idazoxan (4 nM in the presence of 10(-6) M I-epinephrine to prevent binding to alpha-2 adrenoceptors) or [3H]RX821002 (1 nM). Drugs such as cirazoline, guanoxan, naphazoline, tolazoline, clonidine, bromoxidine (UK 14,304) and phenylbiguanide displaced [3H]idazoxan from two distinct binding sites, which suggested the existence of two affinity states for I2-imidazoline sites that were not modulated by MgCl2 or the nucleotide analog guanylyl-5'-imido-diphosphate. Binding affinities at the low-affinity site (KiL) were consistently more than 2 orders of magnitude lower than binding affinities at the high-affinity site (KiH), and there was a good correlation between KiH and KiL values for a given drug in the human (r = 0.89) and rat (r = 0.92) brains. For 18 to 22 drugs, the Ki values in the human brain correlated well with the corresponding Ki values in the rat brain both for I2-imidazoline sites (r = 0.94) and alpha-2 adrenoceptors (r = 0.97). However, the Ki values for I2-imidazoline sites did not correlate with the Ki values for alpha-2 adrenoceptors in human and rat brains. The order of drug potency for the I2-imidazoline sites was: guanoxan (1.3 nM) approximately cirazoline > idazoxan approximately naphazoline > clonidine > phentolamine > RX821002 > (8aR, 12aS, 13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a- decahydro-8H-isoquino[2,1-g]-naphthyridine (RS 15385-197) (> 10 microM). In contrast, the potencies at the alpha-2 adrenoceptor were: RS 1538-197 (0.3 nM) > RX821002 > clonidine > phentolamine > idazoxan approximately naphazoline > guanoxan approximately cirazoline (307 nM). The results demonstrate that I2-imidazoline sites (labeled by [3H]idazoxan) and alpha-2 adrenoceptors are different pharmacological entities with similar characteristics in the human and rat brains. In both species, I2-imidazoline sites are markedly heterogeneous in nature.

Adrenergic alpha-Antagonists↗
PubMed1993

[Fecal excretion and the clearance of alpha 1-antitrypsin in patients with Crohn's disease].

In previous work we defined the normal values of faecal alpha-1 antitrypsin (A1ATF) and their plasmatic clearance (CLAT) in 25 healthy patients. The aim of the present study is to compare these previous results with new results obtained when we applied this test to 30 patients with Crohn's disease (CD). We also show the good performance of the mentioned tests as indicators of the intestinal inflammatory activity. We compare the values of A1ATF and CLAT of healthy patients with those of CD patients. We also compare the Crohn's Disease Activity Index (CDAI) and Simple Index between active and inactive CD patients. Our results show significant differences between A1ATF excretion and CLAT as measured in healthy and CD patients. The relationship between those parameters could be explained by the equation CLAT = 0.325 x A1ATF. Active and inactive CD patients only differ significantly with respect to their leucocytes and C reactive protein values. In our group the A1ATF excretion is larger in CD patients with colonic disease.

Adolescent↗
PubMed1992

Characterization of brain imidazoline receptors in normotensive and hypertensive rats: differential regulation by chronic imidazoline drug treatment.

The binding of [3H]idazoxan in the presence of l-epinephrine was used to characterize and quantitate imidazoline receptors in the brain of spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats before and after chronic imidazoline drug treatment. In the cerebral cortex of WKY and SHR rats, the rank order of potency of imidazoli(di)ne drugs (cirazoline greater than idazoxan greater than naphazoline greater than clonidine much greater than RX821002) competing with [3H]idazoxan showed the specificity for an imidazoline receptor which also appeared heterogeneous in nature. In SHR rats, the density of imidazoline receptors (hypothalamus greater than medulla oblongata greater than cerebral cortex) and proportion of high- and low-affinity sites for the receptor were not different from those in WKY and SD rats, suggesting that the receptor itself is not altered in hypertension. However, chronic treatment with idazoxan and cirazoline (10 and 1 mg/kg, i.p., every 12 h for 7 days) consistently increased (about 35%) the density of imidazoline receptors in the brain of WKY and SD, but not in SHR rats. A similar treatment with RX821002, the 2-methoxy analog of idazoxan, which is a highly selective alpha-2 adrenoceptor antagonist, did not increase the density of brain imidazoline receptors. Moreover, the up-regulation of these receptors induced by cirazoline was still present after alkylation of the alpha-2 adrenoceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. The lack of regulation by idazoxan and cirazoline of the density of imidazoline receptors in the brain of SHR rats suggests the existence of a relevant abnormality in the adaptive process of these receptors in this genetic model of hypertension.

Animals↗
PubMed1992

Heart-lung transplantation in situs inversus. A case report in a patient with Kartagener's syndrome.

After a long history of recurrent chronic pulmonary infections in a 25-year-old woman with Kartagener's syndrome, a heart-lung transplantation was performed. A modified surgical procedure was needed to perform transplantation because of the presence of a situs inversus, which is usually associated with bronchiectasis and sinusitis in this congenital syndrome. A large single atrium was created with both the right and left recipient atria used to facilitate anastomosis with the donor's right atrium. The patient was discharged after resolution of early ventilatory complications and is in good condition 8 months after transplantation.

Adult↗
PubMed1991

Decreased density and sensitivity of alpha 2-adrenoceptors in the brain of spontaneously hypertensive rats.

The specific binding of the agonist [corrected], [3H]clonidine, to neural membranes and clonidine-induced mydriasis were used to evaluate the density and sensitivity [corrected] of alpha 2-adrenoceptors in the brain of spontaneously hypertensive rats (SHR) and sex- and age-matched normotensive Wistar-Kyoto (WKY) rats. In hypertensive rats (SHR) the density of alpha 2-adrenoceptors was reduced in the cerebral cortex, hypothalamus and medulla oblongata (20-27%), as was the dose-pupillary response curve for clonidine (1.8-fold). The results demonstrated that this model of genetic hypertension is associated with desensitization of alpha 2-adrenoceptors in the brain.

Animals↗
PubMed1991

[Microalbuminuria in essential arterial hypertension].

BACKGROUND: The occurrence of microalbuminuria (mAlb) in essential hypertension (HT) was evaluated. METHODS: 100 patients were studied (56 males), with mean age 39 +/- 6 years, body mass index (BMI) 28 +/- 4. 32 had borderline HT, 47 had mild HT and 21 had moderate HT. 74 were in stage I of the WHO and 26 were in stage II. All had normal renal function (creatinine 91 +/- 12 mumol, Clcr 92 +/- 13 ml/m/1.73 m2) and no proteinuria as measured by sulphosalicylic acid. mAlb was immuno-nephelometrically measured in two 24-hour urine samples, and was given as urinary albumin excretion (UAE). In 62 patients, noninvasive ambulatory recording of blood pressure (NIAR) was carried out. In 39, ventricular mass was estimated by echocardiography. RESULTS: UAE was correlated with SPB24h (r = 0.39) and DBP24h, but not with SBP or DBP. UAE was greater in patients with moderate HT than in those with mild or borderline HT (p less than 0.01). UAE was less than 20 mg/24 h in 70 patients (group A) and greater than 20 mg/24 h in 30 (group B). The comparative analysis of the two groups showed different clinical BP values (SBP p less than 0.01; DBP p less than 0.001) and NIAR (SBP 24 h p less than 0.001; DBP 24 h p less than 0.05). In the 47 patients with mild HT the only differential parameter between groups A and B was SBP24h (p less than 0.05). Regarding echocardiographic data, in higher UAE levels a greater left ventricular mass index was found in males (chi-square p less than 0.05). CONCLUSIONS: Increased mAlb is associated with more severe HT. This finding may be helpful for the initial evaluation of hypertensive patients.

Adult↗
PubMed1991

Cardiac tumors: clinical experience and surgical results in 74 patients.

A series of 75 cardiac tumors in 74 patients were operated on at La Pitie Hospital between 1972 and 1989. There were 73 primary and 2 metastatic tumors. Among the benign neoplasms, 58 were myxomas; seven of the nine malignant tumors were primary heart tumors. The mean age of the patients was 48 years (range, 9 to 75 years); 46 patients were female and 28 male. Fifty-seven percent of the patients had congestive heart failure, 13% had chest pain, 17% had neurological symptoms, and only 1 patient was totally asymptomatic. The cardiac tumors were incidental findings in 3 patients. Complete resection was carried out in 66 benign lesions and only four of the malignant tumors. All patients survived operation, although 4 died in the early postoperative period. Long-term results were excellent in patients with benign lesions, and no recurrences were found. In patients with malignant tumors, surgical procedures were only palliative and aimed at prolonging life; hence, prognosis remained unchanged.

Adolescent↗
PubMed1991

Repeated idazoxan increases brain imidazoline receptors in normotensive (WKY) but not in hypertensive (SHR) rats.

The specific binding of [3H]idazoxan in the presence of 10(-6) M (-)-adrenaline was used to evaluate the density of imidazoline receptors in the brain of spontaneously hypertensive (SHR) rats and sex- and age-matched normotensive Wistar-Kyoto (WKY) rats. In SHR rats the density of imidazoline receptors (cerebral cortex, hypothalamus, and medulla oblongata) was not different from that in normotensive (WKY) rats. However, repeated treatment with idazoxan consistently increased (23-80%) the density of imidazoline receptors in the various brain regions of WKY rats but not in SHR rats. In normotensive Sprague-Dawley rats, repeated treatment with the imidazoline drugs idazoxan and cirazoline also increased (33-37%) the density of imidazoline receptors in the cerebral cortex. The lack of regulation by idazoxan of the density of imidazoline receptors in the brain of SHR rats might reflect the existence of a relevant abnormality of these receptors in this genetic model of hypertension.

Adrenergic alpha-Antagonists↗
PubMed1990

Ontogeny of binding sites for [3H] kainic acid in chick and rat cerebellar membranes: a comparative study.

We have analyzed the developmental properties of kainate receptors in cerebellar membranes prepared from chick and rat, two vertebrate species with contrasting patterns of functional maturation. Single populations of binding sites have been characterized in the avian and rodent membranes with apparent dissociation constants (Kd) in the 210-280 nM and 40-55 nM ranges, respectively; the number of binding sites (Bmax) increases with age in both species, reaching a maximum of 187 pmol/mg in the case of 10-day chicks vs. 1.28 pmol/mg in 75-day rats. The ontogenetic profiles of kainate receptors in chick and rat cerebella are in consonance with the patent differences in motor development at birth.

Aging↗
PubMed1990

[Intracardiac myxoma: surgical treatment with trans-septal approach].

In the last 15 years, fifty-two cases of cardiac myxoma underwent surgical excision at La Pitié Hospital-Paris. They were 19 male and 32 female aging from 16 to 75 years (mean 15 +/- 10). Symptoms were congestive heart failure (55%), constitutional syndrome (35%), peripheral embolization (25%) and syncopal episodes (7%). Echocardiographic diagnosis was done in almost all cases. 47 tumors were found in the left atrium, 4 in the right and 1 in the right ventricule. Transeptal approach was used in most of the patients and myxomas were totally removed including a part of atrial septum, requiring patch reconstruction in 35 patients. Postoperative mortality was very low (1.9%). No complications nor recurrences have been reported in the long-term follow-up.

Adolescent↗