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Biomedical subjects

M A Rubio

Publications and source records attributed to M A Rubio.

At least 37 records · Page 2Linked to original sources
PubMed1995

Monocyte activation: rapid induction of alpha 1/beta 1 (VLA-1) integrin expression by lipopolysaccharide and interferon-gamma.

Monocytes play a key role in inflammation, tissue injury and remodelling and wound healing, and most monocyte effector functions are dependent on adhesive interactions. We have analyzed the changes in the pattern of beta 1 integrin expression that take place during monocyte activation and demonstrated that lipopolysaccharide (LPS) and interferon (IFN)-gamma specifically induce the expression of the alpha 1/beta 1 integrin, which was detectable on the monocyte membrane as early as 12 h after monocyte activation. The up-regulated alpha 1/beta 1 expression was not dependent on monocyte adherence to solid surfaces, and Northern blot analysis revealed that LPS and IFN-gamma induce the alpha 1 mRNA de novo. Monocyte deactivating cytokines such as interleukin (IL)-4 or IL-10, could only minimally inhibit the LPS- or IFN-gamma mediated up-regulation of alpha 1/beta 1, suggesting that cytokine release subsequent to monocyte activation does not play a major role in the integrin induction. Interestingly, the LPS-induced expression of alpha 1/beta 1 was found to be dependent on the redox state of the cell, since it was inhibited by antioxidants which also altered the morphological changes that take place during monocyte culture in vitro. The rapid induction of alpha 1 in LPS-activated monocytes suggests that alpha 1/beta 1 might be involved not only in monocyte/extracellular matrix interactions during inflammatory reactions, but also in contributing to further monocyte activation and cytokine production during septic shock syndrome.

Cell Adhesion↗
PubMed1995

Hematopoietic cell-type-dependent regulation of leukocyte integrin functional activity: CD11b and CD11c expression inhibits LFA-1-dependent aggregation of differentiated U937 cells.

To study the influence of the cellular environment on the functional activity of leukocyte integrins and to analyze their involvement in hematopoietic cell differentiation, we have developed stable transfectants of LFA-1, Mac-1, and p150,95 (CD11a-c/CD18) leukocyte integrins in cultured cell lines whose differentiation can be induced in vitro. As on circulating leukocytes, the integrins expressed on U937 or K562 cells were expressed in a constitutively inactive state, as demonstrated by the lack of adhesion to their cellular counterreceptors or soluble ligands, the absence of CD18-dependent intercellular aggregation, and their inability to mediate adhesion to protein-coated plates. However, while leukocyte integrin adhesive functions in U937 cells were induced upon treatment with cellular agonists (e.g., PMA), their function in K562 cells could be upregulated only with activating monoclonal antibodies, demonstrating the cell-type-specific regulation of the adhesive capabilities of the three leukocyte integrins in hematopoietic cellular environment. On the other hand, the expression of either CD11b/CD18 or CD11c/CD18 in U937 myeloid cells before induction of differentiation greatly affected the adhesive phenotype of differentiating cells by abrogating the CD11a/CD18-CD54-dependent homotypic aggregation. Unlike that of mock-transfected U937 cells, differentiation of CD11b/CD18- or CD11c/CD18-transfected U937 cells led to cell adhesion and spreading on the tissue culture plates, with an almost total absence of homotypic aggregates. These results confirm the role of CD11b/CD18 and CD11c/CD18 in myeloid cell adhesion and spreading and suggest that the CD11b/- and CD11c/CD18-mediated recognition of substrate-bound ligands competes or interferes with LFA-1-dependent intercellular adhesion.

Cell Adhesion↗
PubMed1994

Regulated expression of p150,95 (CD11c/CD18; alpha X/beta 2) and VLA-4 (CD49d/CD29; alpha 4/beta 1) integrins during myeloid cell differentiation.

Integrins are a family of cell surface heterodimers which mediate both cell-cell and cell-extracellular matrix interactions and affect cellular differentiation through their signal transduction capacity. Integrin expression is regulated during differentiation as well as by numerous growth factors and cytokines. We have analyzed the changes in p150,95 (CD11c/CD18 or alpha X/beta 2) and VLA-4 (CD49d/CD29 or alpha 4/beta 1) integrin subunits mRNA levels that take place during the myeloid differentiation of HL60 and U937 cells, and compared them to other integrins with similar functional activities. Northern blot analysis revealed that the monocytic differentiation of U937 and HL60 cells alters the alpha X and alpha 4 mRNA steady-state levels: alpha X mRNA is induced de novo whereas alpha 4 mRNA decreases to undetectable levels. Both changes were dependent on the activity of protein kinase C and were also observed upon granulocytic differentiation of HL60 cells. Parallel analysis of other integrin subunits mRNA (beta 1, alpha 5, beta 7) demonstrated that the mRNA levels for the alpha subunits of the fibronectin receptors alpha 4/beta 1 (VLA-4) and alpha 5/beta 1 (VLA-5) are differentially regulated during the monocytic differentiation of myeloid cell lines, and suggested that myeloid cells express a heterodimer formed by the association of beta 7 with an integrin alpha subunit distinct from alpha 4. Nuclear transcription assays and functional analysis of the alpha X and alpha 4 promoter regions demonstrated that the transcription rate of the alpha X gene is considerably elevated after phorbol 12-myristate 13-acetate treatment of U937 cells, while that of alpha 4 is almost unaffected, suggesting that post-transcriptional mechanisms are causing the extremely low alpha 4 mRNA levels observed in differentiated U937 cells.

Blotting, Northern↗
PubMed1993

Pancreatic reserve and insulin dose in type 2 diabetic patients.

In order to determine whether there is any relationship between pancreatic reserve and the insulin dose required for achieving a good metabolic control in type 2 diabetic patients with secondary failure to oral hypoglycaemic agents, fasting and post-glucagon C-peptide were determined in thirty-nine type 2 diabetic patients with secondary failure to sulphonylureas and hyperglycaemia < 250 mg/dl who attended an outpatient clinic. M-value was calculated in patients performing self-monitoring of blood glucose. Otherwise, pre- and post-prandial glycaemias were measured bi-weekly as outpatients. HbA1c and fructosamine were assessed monthly. A patient was considered well controlled when he or she fulfilled all the requirements of the European NIDDM Policy Group and the insulin dose necessary for these goals was correlated to the pancreatic reserve. There were two drop-outs. Thirty-five out of the thirty-seven patients complied with the objectives in an average time of 3.14 +/- 1.93 months. At the beginning of the study mean HbA1c was 8.01 +/- 1.40% and fructosamine 343.81 +/- 59.05 micromol/l, whereas at the end of the study the values were 6.91 +/- 0.94% and 291.89 +/- 38.59 micromol/l, respectively (both p < 0.001). Body weight increased from 68.95 +/- 12.40 to 69.44 +/- 12.54 kg (n.s.), while hypoglycaemic events decreased from 1.70 +/- 2.37 to 0.88 +/- 1.33 events/week (p < 0.05). To attain all the objectives, 19.03 +/- 5.98 i.u. (0.28 +/- 0.08 i.u./kg) of insulin were required. Basal and post-glucagon C-peptide were 1.97 +/- 1.24 and 3.29 +/- 1.85 ng/ml, respectively, with an increase of 1.32 +/- 0.78 ng/ml. All these values inversely correlated with insulin dose, especially the increase during the test (r = -0.652 with i.u./kg and r = -0.599 with i.u., both p < 0.01). In conclusion, C-peptide test is a good indicator of the insulin dose required for achieving the aims of metabolic control in type 2 diabetic patients.

Aged↗
PubMed1992

Mapping of the human VLA-alpha 4 gene to chromosome 2q31-q32.

The integrin VLA-4 (alpha 4: beta 1; CD49d/CD29) is involved in both cellular adhesion to extracellular matrix and cell-cell interactions. We have determined that the human gene coding for VLA-alpha 4 is located on the long arm of chromosome 2 by using fluorescence in situ hybridization. The VLA-alpha 4 gene has been more precisely mapped to the 2q31-q32 region after GTG banding (G-bands by trypsin using Giemsa). These data suggest that the VLA-4 gene belongs to the COL3A1-(ELN-FN)-COL6A3 linkage group and establishes a potential genetic relationship between the alpha 4 and alpha v integrin subunits.

Cell Adhesion↗
PubMed1992

Improvement of the hydrodynamic response of a ventricular assist device: a false auricle solution.

We propose a new design of the auricular cannula in ventricular assist devices (VADs), consisting of a collapsible large cannula with a capacity approximately equal to the ejection volume of the VAD. The device works as a false auricle and filters the negative pressure that occurs during diastole. We show that the use of this type of cannula improves the hydrodynamic efficiency and the stability of the working conditions. Moreover, during chronic implantation in sheep, hemolysis stays well below pathological levels. These improvements result in much better controllability of the whole VAD.

Animals↗
PubMed1991

First clinical implantation of the BCM 3.5 ventricular assist device (VAD).

We report on the first human implantation of the BCM 3.5 ventricular assist device in a 46-year-old man suffering from terminal stage cardiomyopathy. The circulatory support was used as a bridge to heart transplantation. The patient was in cardiogenic shock and was on assisted circulation for 18 days after which he underwent cardiac transplantation. While receiving support from the ventricular assist device, the patient's condition improved remarkably and 50 days after transplantation he was discharged from hospital. We give a detailed description of the surgical technique, with special emphasis on the procedures for air extraction. We describe the evolution of the hemodynamic status before and after implantation. Final inspection of the device and cannulae after removal showed no thrombi and only small fibrin deposits in the membrane-wall junction.

Cardiomyopathy, Dilated↗
PubMed1990

Bacterial metabolism of side-chain-fluorinated aromatics: unproductive meta-cleavage of 3-trifluoromethylcatechol.

Sixteen bacterial strains capable of degrading alkylbenzenes and alkylphenols were directly isolated from soil and water. The degradation pathways are discussed. Alkylcatechols are almost exclusively cleaved via meta-ring fission. Meta-cleavage of 3-trifluoromethyl-(TFM)-catechol was observed with all strains at different rates although the reaction rates compared to catechol as a substrate varied considerably. All 2-hydroxy-6-oxohepta-2,4-dienoic acid hydrolases investigated showed strong binding of 7,7,7-trifluoro-2-hydroxy-6-oxohepta-2,4-dienoic acid, the ring fission product of 3-TFM-catechol. Turnover rates, however, were negligible indicating this compound to be a general dead-end metabolite during metabolism of TFM-substituted compounds via meta-cleavage pathways.

Bacteria↗
PubMed1989

Blood biochemistry values of sheep (Ovis aries ligeriensis).

1. Analysis of biochemical parameters were carried out on material pooled from 30 female sheep (Ovis aries ligeriensis). 2. The values determined were for the common metabolites and enzymes utilized for specific studies in general metabolism (urea, glucose, cholesterol, lipids, bilirubin, uric acid, creatinine, alkaline phosphatase, GOT, GPT, LDH, LAP, CGT, CK and amylase). 3. Results of these studies were compared with values from normal human adults. 4. The differences obtained in human and sheep ranges can be explained by the different physiology of the two species. 5. This study gives values for the sheep as an experimental animal in biomedical research.

Animals↗
PubMed1989

Bacterial metabolism of 2,6-xylenol.

Strain DM1, a Mycobacterium sp. that utilizes 2,6-xylenol, 2,3,6-trimethylphenol, and o-cresol as sources of carbon and energy, was isolated. Intact cells of Mycobacterium strain DM1 grown with 2,6-xylenol cooxidized 2,4,6-trimethylphenol to 2,4,6-trimethylresorcinol. 4-Chloro-3,5-dimethylphenol prevents 2,6-xylenol from being totally degraded; it was quantitatively converted to 2,6-dimethylhydroquinone by resting cells. 2,6-Dimethylhydroquinone, citraconate, and an unidentified metabolite were detected as products of 2,6-xylenol oxidation in cells that were partially inactivated by EDTA. Under oxygen limitation, 2,6-dimethylhy-droquinone, citraconate, and an unidentified metabolite were released during 2,6-xylenol turnover by resting cells. Cell extracts of 2,6-xylenol-grown cells contained a 2,6-dimethylhydroquinone-converting enzyme. When supplemented with NADH, cell extracts catalyzed the reduction of 2,6-dimethyl-3-hydroxyquinone to 2,6-dimethyl-3-hydroxyhydroquinone. Since a citraconase was also demonstrated in cell extracts, a new metabolic pathway with 2,6-dimethyl-3-hydroxyhydroquinone as the ring fission substrate is proposed.

Journal Article↗
PubMed1989

Prolactin-lowering effect of luteinizing hormone-releasing hormone agonist administration in prolactinoma patients.

We studied the effect of LHRH agonist administration on serum PRL levels in five women with microprolactinomas and two women and a man with intrasellar macroprolactinomas. Each patient received either D-Trp6-LHRH or buserelin for 90 days. Serum PRL levels decreased significantly in the patients with microprolactinomas by 65%, from 156 +/- 93 (+/- SD) to 54 +/- 49 micrograms/L on day 90 (P = 0.011), but it did not decrease in the macroprolactinoma patients. Mean serum LH and FSH decreased by 43% and 62.5%, respectively, in all eight patients. There was no statistically significant correlation between the serum PRL and LH or FSH levels in the microprolactinoma patients. We conclude that LHRH agonists can counteract the hyperprolactinemia produced by microprolactinomas and that the effect probably is not exerted by an action on the gonadotrophs.

Adult↗
PubMed1989

Zinc in adult human serum in Spain.

Zinc levels in serum taken from 1,166 healthy, adult volunteers, from 16 to 70-year-olds living in 10 different districts of the Province of Granada (Spain), have been measured by atomic absorption spectrophotometry. The zinc levels ranged from 80 micrograms to 130 micrograms/100 ml. There were no significant differences with regard to age. The overall results showed higher zinc levels for males than for females but this did not appear when the values for each individual district were analysed separately.

Adolescent↗
PubMed1988

Bacterial metabolism of side chain fluorinated aromatics: cometabolism of 4-trifluoromethyl(TFM)-benzoate by 4-isopropylbenzoate grown Pseudomonas putida JT strains.

Enzymes of the p-cymene pathway in Pseudomonas putida strains cometabolized the intermediate analogue 4-trifluoromethyl(TFM)benzoate. Three products, 4-TFM-2,3-dihydro-2,3-dihydroxybenzoate, 4-TFM-2,3-dihydroxybenzoate and 2-hydroxy-6-oxo-7,7,7-trifluorohepta-2,4-dienoate (7-TFHOD) were identified chemically and by spectroscopic properties. Certain TFM-substituted analogue metabolites of the p-cymene pathway were transformed at drastically reduced rates. Hammett type analysis of ring cleavage reactions of 4-substituted 2,3-dihydroxybenzoates revealed the negative inductive and especially mesomeric effect of substituents to be rate determining. Whereas decarboxylation of 3-carboxy-7-TFHOD was not affected by fluorine substitution the subsequent hydrolysis of 7-TFHOD proceeded very slowly. The negative inductive effect of the TFM-group probably inhibited heterolysis of the carbon bond between C5 and C6 of 7-TFHOD.

Benzoates↗