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J Alvarez

Publications and source records attributed to J Alvarez.

At least 181 records · Page 10Linked to original sources
PubMed1994

Structural determinants of the Alzheimer's amyloid beta-peptide.

The hallmark event of Alzheimer's disease (AD) is the deposition of amyloid as insoluble fiber masses in extracellular neuritic plaques and around the walls of cerebral blood vessels. The main component of amyloid is a hydrophobic peptide, named amyloid beta-peptide (beta A4), which results from the processing of a much longer membrane amyloid precursor protein (APP). This review focuses on the structural features of beta A4 and the factors that determine beta A4 insolubilization. Theoretical and experimental studies of the primary structure of beta A4 have shown that it is composed of a completely hydrophobic C-terminal domain, which adopts beta-strand structure, and an N-terminal region, whose sequence permits different secondary structures. In fact, this region can exist as an alpha-helical or beta-strand conformation depending on the environmental condition (pH and hydrophobicity surrounding the molecule). The effects of pH and hydrophobicity on beta A4 structure may elucidate the mechanisms determining its aggregation and amyloid deposition in AD.

Alzheimer Disease↗
PubMed1994

Cardiac T-type calcium current: pharmacology and roles in cardiac tissues.

A low threshold, voltage-gated calcium current is reported in most cardiac tissues but rarely in ventricular cells. This article reports some recently described characteristics and discusses their possible pathophysiologic implications. It also reviews the alterations induced in this current by a variety of chemical agents including several neuromediators in cardiac and other tissues.

Animals↗
PubMed1994

Catecholamine and blood lactate responses to incremental rowing and running exercise.

Ten collegiate rowers performed discontinuous incremental exercise to their tolerable limit on two occasions: once on a rowing ergometer and once on a treadmill. Ventilation and pulmonary gas exchange were monitored continuously, and blood was sampled from a venous catheter located in the back of the hand or forearm for determination of blood lactate ([La]) and plasma epinephrine ([Epi]) and norepinephrine ([NE]) concentrations. Thresholds for lactate (LT), epinephrine (Epi-T), and norepinephrine (NE-T) were determined for each subject under each condition and defined as breakpoints when plotted as a function of O2 uptake (VO2). For running, LT (3.76 +/- 0.18 l/min) was lower (P < 0.05) than Epi-T (4.35 +/- 0.14 l/min) and NE-T (4.04 +/- 0.19 l/min). For rowing, LT (3.35 +/- 0.16 l/min) was lower (P < 0.05) than Epi-T (3.72 +/- 0.22 l/min) and NE-T (3.70 +/- 0.18 l/min) and was lower (P < 0.05) than LT for running. Within each mode of exercise, Epi-T and NE-T did not differ. Because LT occurred at a significantly lower VO2 than either Epi-T or NE-T, we conclude that catecholamine thresholds, per se, were not the cause of LT. However, for both modes of exercise LT occurred at a plasma [Epi] of approximately 200-250 pg/ml (rowing, 221 +/- 48 pg/ml; running, 245 +/- 45 pg/ml); these concentrations are consistent with the plasma [Epi] reported necessary for eliciting increments in blood [La] during Epi infusion at rest. Plasma [NE] at LT differed significantly between modes (rowing, 820 +/- 127 pg/ml; running, 1,712 +/- 217 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Induction of mixed apneas by inhalation of 100% oxygen in preterm infants.

Administration of 100% O2 to preterm infants induces an apnea that is usually central. We hypothesized that this apnea may be "mixed" at times with an obstructive component appearing late during the respiratory pause. In addition, we reasoned that obstruction would depend on the duration of the apnea. Thus, we gave 100% O2 to 61 healthy preterm infants. Group 1 was > or = 1,500 g [birth wt 1.8 +/- 0.1 (SE) kg, gestational age 32 +/- 1 wk, postnatal age 19 +/- 2 days, n = 26] and group 2 was < 1,500 g [birth wt 1.2 +/- 0.1 kg, gestational age 29 +/- 1 wk, postnatal age 30 +/- 4 days, n = 35]. Ventilation was measured using a flow-through system. Respiratory efforts in the absence of flow were detected using chest and abdominal displacements or diaphragmatic electromyography. In group 1, 19% of the central apneas became obstructive at 17 +/- 3 s, whereas in group 2, 34% did so at 12 +/- 2 s. Mixed apneas were longer than those without obstruction (28 +/- 3 vs. 12 +/- 1 s; P = 0.0001). The incidence of mixed apneas was 0, 14, and 66% in group 1 and 0, 27, and 69% in group 2 in apneas of 3-10, 11-20, and > 20 s, respectively. These findings suggest that 1) a percentage of the central apneas induced by inhaling 100% O2 became obstructive, 2) the incidence of the obstructive component increased with the duration of apnea, and 3) smaller infants became obstructed sooner and had a higher incidence of obstruction than larger infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea↗
PubMed1994

Tuberculosis.

Explore the source record for details and available documents.

Developing Countries↗
PubMed1994

One year's experience with an acute pain service in a Spanish University Clinic hospital.

We describe the experience of the acute pain service of the University Hospital of Galicia, Spain since its inception. We have treated 1214 patients using either patient-controlled analgesia (PCA) with morphine (72%), or patient-controlled epidural analgesia with fentanyl + bupivacaine (22%). Three hundred and five patients had minor complications, mainly pruritus (35%) in patients with patient-controlled epidural analgesia. Three (0.33%) patients using PCA had respiratory depression treated with naloxone; no patient with patient-controlled epidural analgesia had respiratory depression. In our experience the creation of an acute pain service and the associated development of pain-treatment protocols and the training of hospital personnel produced excellent results.

Academic Medical Centers↗
PubMed1993

Inhibition of the calcium store-operated calcium entry pathway by chemotactic peptide and by phorbol ester develops gradually and independently along differentiation of HL60 cells.

N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibited transiently the entry of Ca2+ and Mn2+ induced by emptying with thapsigargin the Ca2+ stores of HL60 cells differentiated toward granulocytes. Phorbol 12,13-dibutyrate (PDB) produced a permanent inhibition of this store-operated Ca2+ entry pathway (SOCP), suggesting that inhibition was due to protein phosphorylation mediated by protein kinase C (PKC). Inhibition by PDB was prevented by the PKC inhibitors staurosporin and chelerythrine. Inhibition by fMLP was prevented by chelerythrine but only partially by staurosporin. The characteristics of the inhibition were similar to those reported in human neutrophils (Montero, M., Alvarez, J., and García-Sancho, J. (1993) J. Biol. Chem. 268, 13055-13061). Neither fMLP nor PDB inhibited significantly SOCP in undifferentiated HL60 cells. Single-cell [Ca2+]i measurements at different stages of differentiation showed that inhibition by fMLP and PDB developed independently, suggesting different inhibitory mechanisms. The simplest explanation would be that inhibition by fMLP takes place through activation of a protein kinase distinct from PKC and that the PDB-activated PKC isoform necessary to phosphorylate and inhibit SOCP is expressed only along differentiation. Additionally, inhibition by both fMLP and PDB developed gradually. At intermediate stages of differentiation, PDB was able to produce a partial and maintained inhibition and fMLP a partial and short-lived inhibition of SOCP.

Alkaloids↗
PubMed1993

Platelet of Alzheimer patients: increased counts and subnormal uptake and accumulation of [14C]5-hydroxytryptamine.

Platelets are the main source of 5-hydroxytryptamine (5-HT) and amyloid precursor protein (APP) found in plasma. We studied a possible correlation between platelet markers and the clinical diagnosis of Alzheimer disease (AD). Our results indicate that in AD patients: (a) platelets are elevated, (b) their ability to accumulate 5-HT decreases and, (c) the kinetic parameters of 5-HT uptake are altered (decreased Km and Vmax), compared to non-demented healthy individuals. An aged Down syndrome patient presents even more deviant alterations. Our findings supports the idea that platelets may provide a systemic marker of AD, and eventually be useful for the clinical diagnosis of the disease.

Aged↗
PubMed1993

Dissociation of platelet-activating factor production and arachidonate release by the endomembrane Ca(2+)-ATPase inhibitor thapsigargin. Evidence for the involvement of a Ca(2+)-dependent route of priming in the production of lipid mediators by human polymorphonuclear leukocytes.

The production of platelet-activating factor (PAF) and the release of [3H]arachidonate were studied in human polymorphonuclear leukocytes (PMN) stimulated with thapsigargin, an inhibitor of endomembrane Ca(2+)-ATPase. Concentrations of thapsigargin as low as 10-25 nM primed PMN for both PAF production and [3H]arachidonate release in response to the chemotactic peptide (fMLP), whereas concentrations in the range 25-200 nM induced a time- and dose-dependent production of PAF, which occurred in the absence of both [3H]arachidonate release and [3H]phosphatidylethanol formation. Studies in fura-2/AM-loaded cells showed that concentrations of thapsigargin that elicited PAF production induced a protracted and long lasting elevation of cytosolic free calcium concentration ([Ca2+]i) between 200 and 700 nM. The lower concentrations primed the cells for a late [Ca2+]i elevation in response to fMLP similar to that elicited by cytochalasin B or ionomycin. PAF production showed a good correlation with the increase of [Ca2+]i (r = 0.91) irrespective of the procedure used to grade [Ca2+]i. In contrast, phorbol 12,13-dibutyrate failed to induce both PAF production and elevation of [Ca2+]i, but it was a very effective stimulator of [3H]arachidonate release and [3H]phosphatidylethanol production. These data indicate that PAF production and [3H]arachidonate release in PMN differ in both biochemical pathway and modulatory mechanisms. Whereas PAF production seems extremely sensitive to changes in [Ca2+]i, which seems to exert its modulatory effect at the lyso-PAF:acetyl-CoA acetyltransferase step, [3H]arachidonate release seems tightly modulated by protein kinase C-dependent mechanisms and is coincidental with activation of phospholipase D.

Arachidonic Acid↗
PubMed1993

A neurofilament polypeptide and the glial fibrillary acidic protein share common epitopes in the variable region.

A polyclonal antibody against the high molecular weight neurofilament polypeptide (NF-H) obtained from cytoskeletal extracts of bovine spinal cord reacted with NF-H, with the middle molecular weight neurofilament polypeptide (NF-M) and with a M(r) 51,000 polypeptide, but not with the low molecular weight neurofilament polypeptide (NF-L). The M(r) 51,000 polypeptide corresponded to the glial fibrillary acidic protein (GFAP), which forms the intermediate filaments of astrocytes. The polyclonal antibody affinity-purified with GFAP, reacted with both purified GFAP and NF-H. Digestion of NF-H with alpha-chymotrypsin was used to determine the recognition site of the affinity-purified antibodies. Only fragments of the tail domain of NF-H reacted with the antibody. We propose that common epitopes exist between the variable C-terminal domains of NF-H and GFAP.

Animals↗
PubMed1993

[An epidemic outbreak of measles in a rural area].

OBJECTIVE: Analysis of an outbreak of measles among a partially vaccinated school population: the epidemiology, the effectiveness of the control measures and the efficacy of the vaccine (EV). DESIGN: A descriptive study and cohorts study. SETTING: Primary Care in the borough of Sant Andreu de la Barca. PATIENTS AND OTHERS PARTICIPANTS: The school population of Sant Andreu de la Barca. MEASUREMENTS AND MAIN RESULTS: The outbreak lasted three months and twenty days, with 95 cases overall. The most affected age group was form 4 to 10. 8.4% presented complications. Children were infected at school in 87% of the cases. The overall infection rate of the population between 0 and 15 was 2.4%. 36% of the cases had been correctly immunized and 43% were preventable cases. Vaccine coverage contacts was 67%. 84% of the susceptible contacts were vaccinated. Immunization status and immunization age of 323 out of 500 pupils was studied for the EX analysis. Global EV was 66% (42-80), 58% (13-80) for those immunized, between 12-14 month of age and 71% (43-85) for those immunized after the 15 month of age. CONCLUSIONS: In order to eradicate the autoctonous measles an increase in immunization coverage, an improvement in the epidemiologic surveillance, and in the outbreak control measures are needed.

Adolescent↗
PubMed1993

Transient inhibition by chemotactic peptide of a store-operated Ca2+ entry pathway in human neutrophils.

Emptying the intracellular calcium stores of fura-2-loaded human neutrophils by treatment with the endomembrane ATPase inhibitor thapsigargin leads to a maintained increase of [Ca2+]i by Ca2+ entry through a store-operated Ca2+ entry pathway. Under these conditions, [Ca2+]i was reduced transiently by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and permanently by phorbol 12,13-dibutyrate (PDB). Platelet-activating factor (PAF) had no effect. The fMLP- and PDB-induced [Ca2+]i decreases were not due to stimulated Ca2+ efflux but to inhibition of store-operated Ca2+ entry pathway. PDB and fMLP, but not PAF, inhibited the entry of Ca2+, Mn2+, and Ba2+ in thapsigargin-treated cells. This inhibition was dependent on [Ca2+]i, barely detectable at [Ca2+]i of 50 nM and increasingly strong and fast to appear at 170 and 630 nM. Inhibition of entry by fMLP was complete within 5-10s, disappeared within 2-3 min, and was partially prevented by staurosporin (100 nM). Inhibition by PDB was equally fast, but no recovery was detected within 5 min, and it was fully prevented by staurosporin. The inhibitory effect of fMLP had similar characteristics when PAF was used instead of thapsigargin to induce the entry of Ca2+ or Mn2+. We conclude that fMLP, but not PAF, is able to produce a transient inhibition of store-operated Ca2+ entry pathway, probably mediated by protein kinase C. This action could be part of a general homeostatic mechanism designed to moderate [Ca2+]i increases induced by some agonists.

Biological Transport↗
PubMed1993

Comparative effects of cytochrome P-450 inhibitors on Ca2+ and Mn2+ entry induced by agonists or by emptying the Ca2+ stores of human neutrophils.

The effects of cytochrome P-450 inhibitors of different chemical structures, including several imidazole antimycotics, SKF525A, 5,8,11,14-eicosatetraynoic acid (ETYA), gossypol and nordihydroguaiaretic acid (NDGA), were tested on the entry of Ca2+ and Mn2+ induced either by emptying the intracellular Ca2+ stores with thapsigargin or by stimulation with platelet activating factor (PAF). Most of the drugs inhibited thapsigargin-induced Ca2+ and Mn2+ entry with the same affinity, with the striking exceptions of econazole and miconazole, which were 5- and 2-fold more potent to inhibit the thapsigargin-induced Mn2+ entry than to inhibit Ca2+ entry, respectively. Additionally, high doses of every drug (3-10-times the Ki) activated a pathway permeable to Mn2+ and Ni2+ but not to Ca2+. These findings indicate that Mn2+ entry data should be interpreted with caution and always be cross-checked with Ca2+ uptake measurements. Most of the drugs inhibited PAF-induced Mn2+ uptake with an affinity similar to that found for thapsigargin-induced Mn2+ uptake. PAF- and thapsigargin-induced Ca2+ uptake were also inhibited similarly by NDGA, SKF525A and gossypol, but PAF-induced Ca(2+)-uptake was inhibited about 5-fold more strongly by econazole and ETYA and two-fold more strongly by miconazole and clotrimazole. These findings suggest that the Ca2+/Mn2+ entry pathway opened by agonists in human neutrophils is the same that activates on emptying the Ca2+ stores and that cytochrome P-450 activity may be involved en the activation of the channels.

Calcium↗
PubMed1993

Biosynthesis of platelet-activating factor (PAF) induced by chemotactic peptide is modulated at the lyso-PAF:acetyl-CoA acetyltransferase level by calcium transient and phosphatidic acid.

The chemotactic peptide fMLP (N-formyl-methionyl-leucyl-phenylalanine) induced the production of platelet-activating factor (PAF) by human polymorphonuclear leukocytes (PMN) incubated with cytochalasin B (CB). CoA-independent transacylase showed similar activity in both resting and stimulated PMN, and PAF production only occurred when lyso-PAF:acetyl-CoA acetyltransferase had been converted into the high activity form. PAF formation was coincidental with an increase of the concentration of cytosolic Ca2+ ([Ca2+]i), and with an enhanced formation of 1-O-[3H]alkyl-2-acyl-sn-glycerol. Both fMLP-induced PAF production and the activation of lyso-PAF:acetyl-CoA acetyltransferase were diminished by propranolol. Since several molecular species of phosphatidic acid (PA) produced an inhibition of both PAF production and acetyltransferase activation on intact cells, a portion of the inhibitory effect of propranolol was related to the accumulation of PA. Furthermore, whereas CB increased both the extent and the duration of the fMLP-induced [Ca2+]i transient, propranolol was found to inhibit the CB-induced increase of the [Ca2+]i transient. These data indicate that both the attenuation of [Ca2+]i transient and the accumulation of PA may operate as termination signals for PAF production by actin on lyso-PAF:acetyl-CoA acetyltransferase.

Acetyltransferases↗