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P Valenzuela

Publications and source records attributed to P Valenzuela.

At least 37 records · Page 2Linked to original sources
PubMed1997

Signal transduction mediated by the truncated trkB receptor isoforms, trkB.T1 and trkB.T2.

The trkB family of transmembrane proteins serves as receptors for BDNF and NT-4/5. The family is composed of a tyrosine kinase-containing isoform as well as several alternatively spliced "truncated receptors" with identical extracellular ligand-binding domains but very small intracellular domains. The two best-characterized truncated trkB receptors, designated as trkB.T1 and trkB.T2, contain intracellular domains of only 23 and 21 amino acids, respectively. Although it is known that the tyrosine kinase isoform (trkB.FL) is capable of initiating BDNF and NT-4/5-induced signal transduction, the functional role or roles of the truncated receptors remain enigmatic. At the same time, the potential importance of the truncated receptors in the development, maintenance, and regeneration of the nervous system has been highlighted by recent developmental and injury paradigm investigations. Here we have used trkB cDNA transfected cell lines to demonstrate that both trkB.T1 and trkB.T2 are capable of mediating BDNF-induced signal transduction. More specifically, BDNF activation of either trkB.T1 or trkB.T2 increases the rate of acidic metabolite release from the cell, a common physiological consequence of many signaling pathways. Further, these trkB.T1- and trkB. T2-mediated changes occur with kinetics distinct from changes mediated by trkB.FL, suggesting the participation of at least some unique rate-limiting component or components. Mutational analysis demonstrates that the isoform-specific sequences within the intracellular domains of each receptor are essential for signaling capability. Finally, inhibitor studies suggest that kinases are likely to be involved in the trkB.T1 and trkB.T2 signaling pathways.

Alternative Splicing↗
PubMed1996

Fluctuation of cardiotocographic tracings during labor in fetal growth retardation.

The objective of our study was to analyse the fluctuation of cardiotocographic scores during labor in fetal growth retardation (FGR). The study took place at the University hospital "Principe de Asturias", Alcalá de Henares, Madrid, Spain. 170 at term FGR fetuses and 170 at term fetuses without FGR as control group were compared using modified Fischer scores, which were blindly performed at 3, 5 and 10 cm of cervical dilatation. As results we found out that the mean value of the Fischer score was significantly lower in FGR at 3 cm of cervical dilatation (8.1 +/- 1 vs 8.7 +/- 0.6), as well as at 5 cm (7.6 +/- 0.9 vs 8.1 +/- 0.7) and at 10 cm (6.7 +/- 0.8 vs 7.4 +/- 0.8). Poor prognosis cardiotocograms were also more common in FGR than in the control group in the three cut-offs points studied (7.5% vs 0.6% at 3 cm, 9.8 vs 1.8 at 5 cm and 37.9 vs 11.6 at complete cervical dilatation). The afore mentioned differences were more remarkable as labor advanced. Conclusions are that poor fetal heart rate recordings were detected in FGR at the beginning of labor when compared with control group fetuses and the differences between both groups increased while the labor prolonging.

Adult↗
PubMed1995

Overdose of colchicine in a three-year-old child.

We report the case of a previously healthy girl who developed a multi-systemic failure after an inappropriate dose of colchicine. The patient recovered completely and had no residual effects.

Bone Marrow↗
PubMed1994

Multivariate analysis of determinants of fetal growth retardation.

OBJECTIVE: To analyse the relative effect of the risk factors related to fetal growth retardation (FGR) in the central area of Spain. STUDY DESIGN: This is a case-control survey of 370 full-term gestations. Of the 370 women, 185 were diagnosed with intrauterine growth retardation, and 185 were in the normal group. All came from a central region of Spain. We took into account 25 possible risk factors. RESULTS: In the FGR group we found 12 risk factors with statistical significance in the univariate analysis (tobacco, drugs, low pre-pregnancy weight, low maternal height, little gestational weight gain, excessive physical activity during pregnancy, low socioeconomic status, low educational level, unmarried, urinary infection, mother's haematological changes, and previous infertility). After the multiple logistic regression analysis, five factors were shown to exist as independent risks (tobacco: OR, 23.50; 95% CI, 3.01-183.18; P < 0.01; low pre-pregnancy weight: OR, 4.01; 95% CI, 2.14-7.51; P < 0.001; low socioeconomic status: OR, 2.91; 95% CI, 1.72-4.90; P < 0.001; little gestational weight gain: OR, 2.52; 95% CI, 1.21-5.22; P < 0.05; and urinary infection: OR, 3.83; 95% CI, 1.49-9.87; P < 0.01). CONCLUSIONS: (i) Tobacco, low pre-pregnancy weight and low socioeconomic status are the three main cause-effect factors of relative importance in our sanitary zone for FGR. (ii) Disproportionate FGR is related more to older mothers and maternal previous illness than to the proportionate FRG.

Body Weight↗
PubMed1994

Intrauterine growth retardation: fluctuation of fetal pH measured between beginning and at the completion of labor.

UNLABELLED: The aim of this study was to evaluate the fluctuation of fetal pH in blood samples taken at the beginning of labor and at the moment of birth as related to intrauterine growth retardation syndrome. This is a prospective follow-up of term gestations, of which 41 were diagnosed as intrauterine growth retardation (IUGR) and 61 as normal ones. pH was measured in scalp blood sample at the beginning of the labor and in umbilical artery right after birth in both groups respectively. The rate of decrease of pH value in relation to duration of labor was determined for each case. Our results are: 1) Lower baseline pH were found in the IUGR group (pH 7.32 vs 7.34, p < 0.01), lower arterial blood pH at birth/.23 +/- 0.08 vs 7.27 +/- 0.08, p < 0.05). 2) Faster decrease of the pH during the labor (0.019 unit/hour vs 0.012, p < 0.05) as related to IUGR. CONCLUSION: IUGR fetuses are more acidotic at the beginning of the labor, and the rate of decrease of the fetal pH per unit of time during the labor is faster at least in a theoretical situation nevertheless it will require more studies if any practical applications are thought of.

Acidosis↗
PubMed1993

Stimulation of the adenylyl cyclase activity in human endometrial membranes by VIP and related peptides.

Vasoactive intestinal peptide (VIP) has been shown to stimulate adenylyl cyclase activity in human endometrial membranes. The effect was dependent on the time and temperature of incubation as well as on the concentration of endometrial membrane proteins in the medium. In the presence of 1 microM GTP, half-maximal stimulation of adenylyl cyclase activity was observed at 25.0 +/- 7.0 nM VIP, whereas the maximal activity (at 1 microM VIP) corresponded to an increase of about 140% with respect to basal values (7.5 +/- 0.6 pmol cyclic AMP/min/mg of protein). However, the maximal stimulation of adenylyl cyclase activity was obtained with helodermin (1 microM) that increased the activity by 170% over the basal. The relative potency of VIP-related peptides upon the adenylyl cyclase activity was: helodermin (ED50 = 1.8 +/- 1.4 nM) > VIP (ED50 = 25.0 +/- 7.0 nM) > PHI (ED50 = 725.0 +/- 127.2 nM). Secretin had a faint effect upon the adenylyl cyclase activity and glucagon was completely inefficient at this level. The presence of alpha s and alpha i subunits of G proteins in human endometrium was detected by immunoblot. Preliminary results showed the presence of two classes of 125I-VIP receptors in human endometrial membranes with the following stoichoimetric parameters: high affinity receptor (Kd = 2.0 nM, binding capacity 0.1 pmol VIP/mg protein) and low affinity receptor (Kd = 0.43 microM, binding capacity 13.1 pmol VIP/mg protein). The present results together with the known presence of VIP in human uterus and the actions of this neuropeptide in the adjacent myometrial tissue support the idea that VIP and related peptides may have a role in human endometrium.

Adenylyl Cyclases↗
PubMed1993

Progestin challenge test in postmenopausal patients.

OBJECTIVES: The purpose of this study is to analyze the characteristics of patients identified with the progestin test. METHODS: We administered the progestin challenge test to 157 postmenopausal women and compared the characteristics of the patients who bled, with those who did not. RESULTS: Bleeding occurred in 14.01% of cases and we found that the number of patients who bled were significantly and independently more overweight, had higher levels of plasma estradiol, had a clear presence of superficial cells in the vaginal epithelium and had been menopausal for fewer years than those who did not bleed. CONCLUSIONS: We concluded that the test identifies women at risk from hormone-related endometrial cancer.

Endometrial Neoplasms↗
PubMed1993

Use of artificial sphincter to bowel segment using rectus muscle interposition.

The use of artificial urinary sphincter around the urethra or bladder neck for the management of urinary incontinence secondary to intrinsic urethral sphincter deficiency is now well accepted. However, its use around the bowel to serve as a sphincter in urinary pouches is still anecdotal. Its use in experimental models has been met with failure because of ischemic bowel necrosis at the cuff site. To obviate these difficulties, a new technique was devised using a flap of rectus muscle that acted as a cushion between the cuff and the bowel wall. Results in five dogs showed that bowel wall ischemia is avoided with cuff pressure of 51-60 cm applied constantly for four weeks while providing pressure to leak around the closed cuff with a pressure of 62-75 cm water. Further study is needed to confirm the long-term effect of this technique on the bowel wall and the ability of the sphincter to maintain continence.

Abdominal Muscles↗
PubMed1993

[Efficacy and secondary effects of chronic treatment with amiodarone].

Long-term therapy with amiodarone has been associated with a high incidence of adverse side effects, that precludes its indication for common cardiac arrhythmias. We have prospectively studied 218 patients (pts), aged 32-87 years, under chronic amiodarone therapy that were followed for 2 years and evaluated for efficacy and adverse side effects. Previous amiodarone treatment ranged from 1 to 135 months. Cardiac arrhythmias were paroxysmal AF (PAF) in 120 pts, sustained VT (SVT) in 36 pts, paroxysmal supraventricular tachycardia (PSVT) in 21 pts, unsustained VT (UVT) in 18 pts and miscellaneous in 23 pts. Amiodarone doses ranged from 500 to 4200 mg per week. Amiodarone was effective in 65% of all patients. No difference was observed between efficacy and type of arrhythmia. Dermatologic toxicity was found in 36%, neurologic toxicity in 23%, thyroid toxicity in 13.4% and pulmonary fibrosis en 2.5% of pts. Amiodarone was discontinued routinely when pulmonary toxicity was present. We conclude that amiodarone therapy is effective in a wide spectrum of arrhythmias. Although drug therapy was associated with a high incidence of adverse side effects, these did not preclude continuation of treatment.

Adult↗
PubMed1991

Molecular cloning of a human basic fibroblast growth factor receptor cDNA and expression of a biologically active extracellular domain in a baculovirus system.

A cDNA clone encoding a human fibroblast growth factor (FGF) receptor was isolated from a hepatoma cell line cDNA library. The cDNA encodes a three immunoglobulinlike-domain FGF receptor that is similar to a human placental FGF receptor cDNA but lacks two amino acids. The variation observed at these two amino acids, also seen in the two immunoglobulinlike-domain FGF-receptors, can be explained by an alternate splicing mechanism. We have used a baculovirus expression system to produce high levels of a soluble, extracellular domain form of the FGF receptor (EC-FGF receptor). Spodoptera frugiperda (Sf9) insect cells infected with recombinant EC-FGF receptor viruses synthesized and secreted an EC-FGF receptor of apparent Mr = 58,000. The EC-FGF receptor purified from conditioned media of infected Sf9 cells by lentil lectin affinity chromatography was shown to bind basic FGF with high affinity (Kd = 1-5 nM), to inhibit the binding of radioiodinated basic FGF to its high affinity receptor and to inhibit endothelial cell proliferation. Furthermore, binding of basic FGF to the EC-FGF receptor was shown to be significantly enhanced by heparin. The availability of biologically active FGF receptors will allow an analysis of their interaction with members of the FGF family of proteins and viruses of the herpes family that have been shown to use the FGF receptor system for cell entry.

Amino Acid Sequence↗
PubMed1990

Effects of captopril versus milrinone therapy in modulating the adrenergic nervous system response to exercise in congestive heart failure.

The potential adverse consequences of increased adrenergic nervous system activity in patients with heart failure are now recognized. Modulation of the plasma noradrenaline response to submaximal exercise should be desirable. The long-term (9 weeks) effects of milrinone (10 mg 4 times a day) or captopril (50 mg 3 times a day) compared to placebo were evaluated in a double-blind crossover study, in 16 patients with stable, congestive heart failure receiving digoxin and furosemide. After treatment, clinical status (score range 0 to 14 points) improved significantly with both milrinone (4.4 +/- 0.5, p less than 0.01) and captopril (4.1 +/- 0.4, p less than 0.01). Plasma noradrenaline at rest was similar with both drugs and not significantly different from placebo. During submaximal exercise it increased significantly to 1,228 +/- 58 pg/ml with placebo and to 1,295 +/- 174 pg/ml with milrinone; this response was reduced significantly with captopril, to 820 +/- 100 pg/ml (p less than 0.01). Thus, long-term therapy with both captopril and milrinone improved the clinical score, but only captopril reduced the plasma noradrenaline response to submaximal exercise. These findings suggest that angiotensin-enzyme inhibition with captopril will modulate the adrenergic system response to daily activities in patients with chronic congestive heart failure and therefore could have additional salutary effects beyond vasodilatation.

Aged↗
PubMed1990

Hepatitis A, B, C, D and E viruses: structure of their genomes and general properties.

Hepatitis A virus is an enteric picornavirus. Its genome is a single stranded RNA molecule of positive-strand polarity of 7478 bases. This sequence codes for a polyprotein which is processed to give rise to viral proteins VP-1, VP-2, VP-3 and others. Hepatitis B virus, a major worldwide infectious and cancer promoting agent contains a DNA genome of 3226 base pairs that replicates by a reverse transcriptase via an RNA intermediate. Extensive sequencing and expression experiments have revealed four major genes named surface, core, polymerase and X which are coded in more than one reading frame. Furthermore, within a frame, proteins are expressed from multiple initiation codons resulting in several related products. The viral genome of hepatitis C virus (nonA-nonB), an elusive major infectious agent, has recently been cloned. This genome is a single positive-stranded RNA of at least 10,000 bases which codes for several antigens, some of them associated specifically with nonA-nonB hepatitis infections. The hepatitis D (delta) viral agent, an infectious agent requiring a hepadnarious for propagation, contains a covalently closed circular single-stranded RNA genome of 1167 nucleotides. This genome encodes the protein p24 and p27 that bind specifically to antisera from patients with chronic hepatitis D infections.

Genes, Viral↗
PubMed1989

Expression of three recombinant homodimeric isoforms of PDGF in Saccharomyces cerevisiae: evidence for difference in receptor binding and functional activities.

Three recombinant homodimeric isoforms of platelet-derived growth factor (PDGF) were produced and purified in milligram quantities by expression of PDGF A- and B-chains in yeast cells. Structural analysis of the purified short and long variants of PDGF-AA (PDGF-AAS and PDGF-AAL) and PDGF-BB showed that they had been properly processed and assembled into dimers. PDGF-AAS and PDGF-AAL were found to bind only to the PDGF A-type receptor on human fibroblasts, with affinities of 0.1 and 0.2 nM, respectively. PDGF-BB bound to cells with A- and B-type receptors and to cells with B-type receptor only with affinities of 0.6 nM in both cases. Each fibroblast appeared to express about 4-5 times more B-type receptors than A-type receptors. The maximal mitogenic response to PDGF-BB of human fibroblasts was almost 2-fold higher than that induced by either of the two PDGF-AA forms. The three isoforms of PDGF also stimulated growth in soft agar of human fibroblasts with PDGF-BB inducing a higher maximal response.

Base Sequence↗