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Biomedical subjects

M Izquierdo

Publications and source records attributed to M Izquierdo.

At least 73 records · Page 4Linked to original sources
PubMed1997

Antiphospholipid antibodies in patients with eosinophilia myalgia and toxic oil syndrome.

OBJECTIVE: To explore whether antiphospholipid antibodies (aPL) are markers of vascular related damage or merely evidence of toxic related autoimmunity, we investigated the presence of different aPL in patients with toxic oil syndrome (TOS) and compared the profile with patients with eosinophilia myalgia syndrome (EMS). METHODS: Reactivity against cardiolipin, P-serine, P-inositol, and P-choline was investigated by ELISA in the blood of 266 patients with acute and chronic TOS, 25 healthy relatives of TOS patients, and 48 patients with EMS. RESULTS: 32% of TOS and 13% of EMS patients had IgG antibodies against cardiolipin and other polyanions. 20% of both TOS and EMS patients presented IgM antibodies against anionic and zwitterionic phospholipids. 36% of TOS healthy relatives had IgM antibodies against differently charged phospholipids. Among 200 patients with chronic TOS, there was no significant association between antibodies and clinical manifestations. CONCLUSION: aPL with different specificity are present in a high percentage of patients with TOS and EMS. The significance of these antibodies remains unclear.

Antibodies, Antiphospholipid↗
PubMed1997

Gene therapy.

Explore the source record for details and available documents.

Animals↗
PubMed1996

Stimulation of phosphatidylinositol turnover is a key event for Fas-dependent, activation-induced apoptosis in human T lymphocytes.

We have analyzed the requirements for activation-induced apoptosis in Jurkat T cells expressing the heterologous human muscarinic type 1 receptor (HM1R; J-HM1-2.2 cells) that is coupled to phosphatidylinositol turnover through a protein tyrosine kinase-independent, G protein-regulated mechanism. Triggering of HM1R with the agonist carbachol is sufficient to induce apoptosis in J-HM1-2.2 cells. Apoptosis is also induced in J-HM1-2.2 cells by triggering of the TCR. Calcium influx, intracellular Ca2+ increase, calcineurin function, and de novo protein synthesis are necessary for receptor-controlled apoptosis. However, blocking protein kinase C with a specific inhibitor does not abrogate receptor-induced apoptosis. Furthermore, HM1R-induced apoptosis is inhibited by blocking Fas ligand/Fas interaction with an antagonist anti-Fas Ab, and Fas ligand mRNA and protein are expressed in J-HM1-2.2 cells stimulated through the HM1R. Therefore, protein tyrosine kinase activation is not an absolute requirement for receptor-controlled Fas ligand expression. Taken together, the results demonstrate that stimulation of phosphatidylinositol turnover can induce apoptosis through a Fas-dependent mechanism that requires calcineurin stimulation, but not protein kinase C activation.

Apoptosis↗
PubMed1996

Correlation-peak imaging.

Identification and quantitation in conventional 1H spectroscopic imaging in vivo is often hampered by the small chemical-shift range. To improve the spectral resolution of spectroscopic imaging, homonuclear two-dimensional correlation spectroscopy has been combined with phase encoding of the spatial dimensions. From the theoretical description of the coherence-transfer signal in the Fourier-transform domain, a comprehensive acquisition and processing strategy is presented that includes optimization of the width and the position of the acquisition windows, matched filtering of the signal envelope, and graphical presentation of the cross peak of interest. The procedure has been applied to image the spatial distribution of the correlation peaks from specific spin systems in the hypocotyl of castor bean (Ricinus communis) seedlings. Despite the overlap of many resonances, correlation-peak imaging made it possible to observe a number of proton resonances, such as those of sucrose, beta-glucose, glutamine/glutamate, lysine, and arginine.

Ricinus communis↗
PubMed1996

[Diaphragm paralysis as a complication of internal jugular vein puncture].

Rare complications of using the internal jugular vein for vascular access are related to puncture of neighboring organs or other structures. We report the atypical case of a 55-years-old woman with unilateral diaphragm paralysis attributed to accidental damage of the phrenic nerve during an attempt to canalize the internal jugular vein. Other more common causes were ruled out. The severe restrictive ventilatory changes produced had only minor clinical and gasometric repercussions, as previous function was normal and no acute or chronic respiratory disease was present. When ventilation is already compromised, however, this event could seriously worsen the patient's condition.

Female↗
PubMed1996

Human malignant brain tumor response to herpes simplex thymidine kinase (HSVtk)/ganciclovir gene therapy.

Growing cells from human brain tumors have been treated in vitro and in vivo with murine therapeutic retroviral producer cells. The therapeutic retrovirus carried the potential suicide gene thymidine kinase (tk) from the herpes simplex virus (HSV). After a few days, in which a large proportion of the tumoral cells had the opportunity to acquire a copy of the retrovirus, treatment with ganciclovir was initiated and considered responsible for considerable cell death both in vitro and in vivo. The in vivo experiments were performed in five adult patients who had failed standard therapy and were expected to survive only a few weeks.

3T3 Cells↗
PubMed1995

Plant histochemistry by correlation peak imaging.

Using a new NMR correlation-peak imaging technique, we were able to investigate noninvasively the spatial distribution of carbohydrates and amino acids in the hypocotyl of castor bean seedlings. In addition to the expected high sucrose concentration in the phloem area of the vascular bundles, we could also observe high levels of sucrose in the cortex parenchyma, but low levels in the pith parenchyma. In contrast, the glucose concentration was found to be lower in the cortex parenchyma than in the pith parenchyma. Glutamine and/or glutamate was detected in the cortex parenchyma and in the vascular bundles. Lysine and arginine were mainly visible in the vascular bundles, whereas valine was observed in the cortex parenchyma, but not in the vascular bundles. Although the physiological significance of these metabolite distribution patterns is not known, they demonstrate the potential of spectroscopic NMR imaging to study noninvasively the physiology and spatial metabolic heterogeneity of living plants.

Journal Article↗
PubMed1995

Activation-induced apoptosis in Jurkat cells through a myc-independent mechanism.

Apoptosis can be induced in the human leukemic T-cell line Jurkat when these cells are stimulated by several known T-cell activators. Among the stimuli that activate Jurkat cells, calcium ionophore A23187, phytohemagglutinin and cross-linked monoclonal antibody anti-CD3 are the best inducers of apoptosis. The activator of protein kinase C phorbol-12,13-dibutyrate causes a rapid but transient stimulation of DNA fragmentation and cell death, and soluble monoclonal antibody anti-CD3 has no effect. Furthermore, apoptosis is delayed when Jurkat cells are stimulated simultaneously with calcium ionophore and phorbol ester. We have analysed the mechanism underlying the induction of apoptosis by these agents and found that down-regulation of c-myc expression by pretreatment with the DNA binding antibiotic mithramycin, an inhibitor of c-myc transcription, does not prevent the activation of the apoptotic process. In the light of these results we can conclude that in these leukemic T-cells, activation of apoptosis may occur by a mechanism independent of c-myc expression.

Antibodies, Monoclonal↗
PubMed1995

[The prevalence of tuberculous infection in the 6- to 7-year-old schoolchild population in Albacete].

To analyze the prevalence of tuberculosis infection, tuberculin tests were given to 3,292 elementary school children in the first and second grades in the environs of Albacete (Spain) in 1992. There were 1,532 children aged 6 (122 vaccinated with BCG) and 1,760 children aged 7 (162 vaccinated); 51 children tested positive (20 who had been vaccinated and 31 who had not been). The prevalence of infection was 0.78% at 6 years of age and 1.25 at 7 years of age in non vaccinated children, a rate similar to that found by earlier national surveys. One case of active pulmonary tuberculosis was identified. Inclusion of the 8.6% who had been vaccinated caused significant distortion of the initial prevalences. The annual rate of infection, estimated based on an annual decline of 4%, was 0.143 %. Differences in tuberculosis infection by family socioeconomic level, as indicted by level of parental studies or place of residence, were not statistically significant, although we did observe a slightly greater rate among children living in poorer areas and with parents with only elementary school education. Our results confirm a downward trend in the prevalence of tuberculosis infection in the population studied, as well as the importance of carrying out this type of survey to provide a reference for active control and for taking an active stand.

Chi-Square Distribution↗
PubMed1995

Long-term rat survival after malignant brain tumor regression by retroviral gene therapy.

Total regression of malignant brain tumors was observed in Wistar rats after retrovirus-mediated gene therapy. Tumors were induced by inoculation of C6 rat glioblastoma cells to a specific location in the rat brain and the tumors that developed were visualized by magnetic resonance imaging (MR). Retroviral vectors were constructed from a defective murine retrovirus to which the thymidine kinase (tk 1) gene from herpes simplex was added (HSV1tk). The vectors produced therapeutic viruses upon their introduction into retrovirus packaging cells. Delivery of the producer cells to the tumor mass and subsequent antiherpetic treatment eradicated the tumors completely, as observed using MRI. Some of the treated animals have been followed for over 8 months and show no signs of recurrence.

Animals↗
PubMed1994

The role of Raf-1 in the regulation of extracellular signal-regulated kinase 2 by the T cell antigen receptor.

Triggering of the T cell antigen receptor (TCR) complex activates the serine/threonine kinase Raf-1 whose function is necessary for TCR induction of the interleukin 2 gene. Raf-1 has been identified as a candidate mitogen-activated protein (MAP) kinase kinase kinase (MKKK) and thus has the potential to couple the TCR to the activation of the MAP kinases such as ERK2. In the present study, the role of Raf-1 in ERK2 regulation of ERK2 in T cells has been explored. A constitutively active Raf-1 kinase, v-raf, or a dominant inhibitory Raf-1 mutant were expressed transiently from the pEF BOS vector in Jurkat cells and the effects of these Raf-1 mutants on a coexpressed ERK2 reporter was assessed. The action of the constitutively active Raf-1 was to stimulate the ERK2 kinase, whereas the dominant negative version of Raf-1 inhibited the ERK2 activation induced by triggering of the TCR. These data indicate a role for Raf-1 in the regulation of ERK2 in T cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1994

The role of protein kinase C in the regulation of extracellular signal-regulated kinase by the T cell antigen receptor.

The aim of this study was to explore the role of protein kinase C (PKC) in the activation of mitogen-activated protein kinases (MAPK) in T lymphocytes. The MAPK extracellular signal-regulated kinase-2 (ERK2) is activated in response to phorbol esters which stimulate PKC, by transient expression of a constitutively active ras mutant by cell activation via the G protein-coupled type 1 muscarinic acetylcholine receptor (HM1R) or in response to triggering of the T cell antigen receptor (TCR). The relative contribution of PKC to TCR and HM1R regulation of ERK2 was explored by examining the effects of a PKC inhibitor (Ro 31-8425) on ERK2 activation. The data demonstrate that phorbol ester and HM1R regulation of ERK2 was prevented by the PKC inhibitor, but that the inhibitor had no effect on ERK2 activation induced by expression of a constitutively active ras mutant p21v-Ha-ras. Furthermore, the TCR stimulates both PKC and p21ras but TCR regulation of ERK2 was only weakly suppressed by the PKC inhibitor. These data indicate that PKC has a potential but not a predominant role in TCR regulation of ERK2.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1994

Ubiquitin genes and ubiquitin protein location in polytene chromosomes of Drosophila.

Ubiquitin genes are found in Drosophila either as a repeat block or as gene fusions with ribosomal proteins. Here is described the location of a new repeat block in the X chromosome that is present in the strain Canton S but absent in Vallecas. There are also two ubiquitin-ribosomal protein fusion genes located at regions 97A of chromosome 3R and 31E of 2L. Using an anti-ubiquitin antibody in Drosophila polytene chromosomes it is shown that ubiquitin is mainly associated with the compact and stabilized structure that forms the bands rather than with the more decondensed and destabilized protein-DNA structure that forms interbands and puffs.

Animals↗
PubMed1993

p21ras couples the T cell antigen receptor to extracellular signal-regulated kinase 2 in T lymphocytes.

It has previously been shown in T cells that stimulation of protein kinase C (PKC) or the T cell antigen receptor (TCR) induces the rapid accumulation of the active guanosine triphosphate-bound form of p21ras. These stimuli also induce the activation of extracellular signal-regulated kinase 2 (ERK2), a serine/threonine kinase that is rapidly activated via a kinase cascade in response to a variety of growth factors in many cell types. In this study, we show that p21ras is a component of the TCR signaling pathway that controls ERK2 activation. In the human Jurkat T cell line, transient expression of constitutively active p21ras induces ERK2 activation, measured as an increase in the ability of an ERK2-tag reporter protein to phosphorylate myelin basic protein. Thus, constitutively active p21ras bypasses the requirement for PKC activation or TCR triggering to induce ERK2 activation. In addition, activation of PKC or the TCR produces signals that cooperate with activated p21ras to stimulate ERK2. Conversely, expression of a dominant negative mutant of ras, Ha-ras N17, blocks ERK2 activation after TCR stimulation, indicating that endogenous p21ras function is necessary for the TCR-stimulated ERK2 activation. Taken together, these results demonstrate that the activation of p21ras is both necessary and sufficient to induce ERK2 activation in T cells.

Enzyme Activation↗
PubMed1993

De novo methylation causes a tissue-specific polymorphic EcoRI pattern at the human epidermal growth factor receptor gene.

A novel restriction polymorphism, probably due to tissue-specific methylation, has been identified at the human epidermal-growth-factor-receptor (EGF-R) gene. DNA isolated from smooth muscle showed altered EcoRI restriction bands when hybridized with different fragments of the EGF-R cDNA. These bands were absent in brain or leucocyte DNA samples from the same individuals. Three restriction sites, partly resistant to cleavage by EcoRI, were characterized in muscle DNA which were not clustered but instead were scattered along the gene. The flanking sequences of one of these resistant EcoRI sites were determined. This specific EcoRI site was followed by a 3'-guanosine generating a methylatable EcoRI sequence. This suggests that the failure to digest to completion these EcoRI sites was due to modification by methylation. In addition, we noted that EcoRI sites were affected at both alleles, indicating that de novo methylation changes, and not methylation events related to genomic imprinting, would cause the muscle-specific EcoRI pattern. Also abnormal restriction fragments with XbaI were observed in muscle DNA. A large number of unrelated muscle DNA samples have been analysed, and all of them displayed an identical EcoRI polymorphic pattern, suggesting that DNA modification by de novo methylation events could be functionally relevant.

Base Sequence↗
PubMed1993

Protein tyrosine kinases couple the interleukin-2 receptor to p21ras.

The T cell growth factor interleukin-2 (IL-2) induces p21ras activation in T lymphocytes. We have previously shown that a protein kinase C (PKC)-mediated pathway for p21ras regulation exists in T cells and that the IL-2 receptor (IL-2R) can couple to p21ras independently of the presence of the PKC pathway for p21ras regulation. Our data show that in conditions where cellular protein tyrosine kinases (PTK) were efficiently down-regulated by pretreatment with the specific PTK inhibitor herbimycin, the IL-2-induced activation of p21ras was blocked. Herbimycin did not inhibit the PKC-mediated pathway for p21ras regulation. Thus, the data indicate that PTK are involved in the coupling of the IL-2R to p21ras.

Benzoquinones↗
PubMed1993

Regulation of PtdIns-3-kinase and the guanine nucleotide binding proteins p21ras during signal transduction by the T cell antigen receptor and the interleukin-2 receptor.

The T cell antigen receptor (TCR) and the interleukin-2 receptor (IL-2R) are important receptors in haematopoiesis since they control the activation and growth of T lymphocytes, respectively. The term T cell activation refers to the events that occur as T cells progress from the G0 to the G1 phase of the cell cycle and is characterised by the production of a wide range of cytokines and other immunomodulators crucial for the growth and development of other haematopoietic cells. Activation also induces the T cells to express on their cell surface high affinity receptors for various cytokines which enable the T cell to respond to the different cytokines generated during an immune response. One well characterised event that occurs when mature T cells are activated is the production of the cytokine IL-2 and the acquisition by the T cell of high affinity IL-2 receptors. Interaction between IL-2 and its cellular receptor than direct T cell growth. One notable difference between TCR and IL-2R signal transduction is that the TCR regulates intracellular calcium and stimulates protein kinase C whereas the IL-2 receptor does not. The present review focuses on TCR and IL-2R regulation of two common intracellular signalling pathways: the regulation of a PtdIns-3-kinase and the activation of the guanine nucleotide binding proteins p21ras. The aim is to illustrate differences in the mechanisms that couple the TCR and IL-2R to these two signalling pathways and attempt to explain the apparent discrepancy of TCR and IL-2R regulation of shared signal transduction pathways even though these receptors mediate quite distinct biological responses.

Animals↗