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Biomedical subjects

J Alvarez

Publications and source records attributed to J Alvarez.

At least 217 records · Page 12Linked to original sources
PubMed1992

Axonal sprouting induced in the sciatic nerve by the amyloid precursor protein (APP) and other antiproteases.

Protease inhibition is the mechanism by which some trophic factors promote the extension of neurites. In the rat sciatic nerve, we assessed the ability to induce sprouts of the APP isoform that embodies the Kunitz antiprotease domain and other antiproteases. With the electron microscope, axonal sprouts were found when antiproteases were supplied but not after administration of inactive substances. We conclude that axons have a drive to sprout which can be released by the unbalance of an extracellular protease-antiprotease system. We propose that this system is involved in the pathogenesis of Alzheimer's disease.

Amyloid beta-Protein Precursor↗
PubMed1992

High affinity inhibition of Ca(2+)-dependent K+ channels by cytochrome P-450 inhibitors.

The Ca(2+)-dependent K+ channel of human red cells was inhibited with high affinity by several imidazole antimycotics which are potent inhibitors of cytochrome P-450. IC50 values were (in microM): clotrimazole, 0.05; tioconazole, 0.3; miconazole, 1.5; econazole, 1.8. Inhibition of the channel was also found with other drugs with known cytochrome P-450 inhibitory effect. However, no inhibition was obtained with carbon monoxide (CO). This suggests that, given the high selectivity of the above inhibitors for the heme moiety, a different but closely related to cytochrome P-450 kind of hemoprotein may be involved in the regulation of the red cell Ca(2+)-dependent K+ channel. Clotrimazole also inhibited two other charybdotoxin-sensitive Ca(2+)-dependent K+ channels, those of rat thymocytes (IC50 = 0.1-0.2 microM) and of Ehrlich ascites tumor cells (IC50 = 0.5 microM). Imidazole antimycotics inhibit also receptor-operated Ca2+ channels (Montero, M., Alvarez, J. and García-Sancho, J. (1991) Biochem. J. 277, 73-79). This suggests that both Ca2+ and Ca(2+)-dependent K+ channels might have a similar regulatory mechanism involving a cytochrome.

Animals↗
PubMed1992

LEAFY controls floral meristem identity in Arabidopsis.

The first step in flower development is the generation of a floral meristem by the inflorescence meristem. We have analyzed how this process is affected by mutant alleles of the Arabidopsis gene LEAFY. We show that LEAFY interacts with another floral control gene, APETALA1, to promote the transition from inflorescence to floral meristem. We have cloned the LEAFY gene, and, consistent with the mutant phenotype, we find that LEAFY RNA is expressed strongly in young flower primordia. LEAFY expression procedes expression of the homeotic genes AGAMOUS and APETALA3, which specify organ identify within the flower. Furthermore, we demonstrate that LEAFY is the Arabidopsis homolog of the FLORICAULA gene, which controls floral meristem identity in the distantly related species Antirrhinum majus.

Amino Acid Sequence↗
PubMed1992

[Diagnosis of dominant renal polycystosis in adults by analysis of DNA polymorphism].

BACKGROUND: Adult renal polycystosis (ARP) is a dominant autosomic disease. The gene responsible for this disease in most families has been located on the short arm of chromosome 16 (16 p) by restriction analysis of the DNA polymorphisms (RFLP). METHODS: The existence of several polymorphic markers flanking this gene permits the diagnosis of any member of an affected family. A series of proximal and distal genetic markers have been used to study the segregation of the disease in a group of families with more than one affected member. RESULTS: The clinical and genetic results obtained from a study of 10 Spanish families with ARP have been reported. A high percentage of the members under 30 years of age (40%) did not present renal cysts. CONCLUSIONS: Restriction analysis of DNA are fundamentally for a disease in which a high percentage of carriers remain asymptomatic within the reproductive age.

Adult↗
PubMed1992

Cytochrome P450 may regulate plasma membrane Ca2+ permeability according to the filling state of the intracellular Ca2+ stores.

The filling state of the intracellular Ca2+ stores of rat thymocytes regulates plasma membrane permeability to Mn2+, used here as a Ca2+ surrogate for plasma membrane Ca2+ channels. Emptying of the Ca2+ stores accelerated Mn2+ entry about 10-fold, and refilling with Ca2+ restored low Mn2+ permeability. The acceleration of Mn2+ entry observed in cells with empty intracellular Ca2+ stores was prevented by cytochrome P450 inhibitors. Imidazole antimycotics, especially econazole and miconazole, were the most potent inhibitors (IC50 approximately equal to 10(-6) M). The inhibitor sensitivity profile was similar to IA-type cytochrome P450. Calmodulin antagonists increased the plasma membrane permeability to Mn2+ in cells with filled Ca2+ stores, and this effect was also blocked by imidazole antimycotics. On this basis, we propose a model in which activation of a cytochrome P450, situated at the Ca2+ stores, opens a plasma membrane Ca2+ pathway. This activity would be inhibited by Ca2+ inside the stores by a calmodulin-dependent mechanism.

Animals↗
PubMed1992

Steroid-resistant asthma: immunologic and pharmacologic features.

Glucocorticoids play an important role in asthma therapy; however, a subset of patients are poorly responsive. We evaluated immunologic and pharmacologic features of 17 patients with steroid-resistant (SR) asthma (six male and 11 female patients) between the ages of 16 and 69 years (mean age, 29 years). SR asthma was defined as failure to improve morning prebronchodilator FEV1 greater than 60% predicted after a 2-week course of oral prednisone (mean dose, 45 mg/day). These patients were compared to 24 steroid-sensitive (SS) patients, aged 5 to 70 years (mean age, 17 years; 17 male and seven female patients), and 47 healthy control subjects, aged 20 to 40 years. Mean prednisone dose in SS patients was 25 mg/day. Steroid pharmacokinetics were evaluated in six patients with SR asthma. All studies were within normal limits. Peripheral blood mononuclear cells (PBMCs) from all subjects were stimulated with 10 micrograms/ml of phytohemagglutinin and incubated for 72 hours with 10(-5) to 10(-9) mol/L of methylprednisolone (Mpn). The Mpn dose-response curve for PBMCs from patients with SR asthma demonstrated a significant (p less than 0.05) increase in DNA synthesis, that is, more T cell proliferation than PBMCs stimulated with phytohemagglutinin in the presence of Mpn, as compared to SS patients and normal subjects. This augmentation of DNA synthesis was reversible with 10 micrograms/ml of troleandomycin in vitro. We conclude that PBMCs from patients with SR asthma demonstrate altered response to Mpn in the presence of a T cell mitogen. This abnormality in cellular response may contribute to persistent airway inflammation in patients with SR asthma despite glucocorticoid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The educational antecedents of teen fatherhood.

In attempting to identify the determinants of teen pregnancy, researchers have focused on risk factors for young women, largely ignoring teen fathers. This study examines the educational antecedents of teen fatherhood using the 1958 National Child Development Study. Results suggest that those less than 20 years old at onset of fatherhood are much more likely than those who had not fathered a child by age 23 to have experienced academic difficulties and that such difficulties antedate teen fatherhood by as much as a decade. Variables measuring parents' lack of interest in their sons' education were strongly associated with the risk of teen fatherhood as were teachers' negative assessment of boys' academic ability, and the boys' own desire to terminate education as early as possible. Social class was modestly important in explaining differences in educational experiences for teen fathers and non-fathers.

Adolescent↗
PubMed1992

Genetic and clinical studies in autosomal dominant polycystic kidney disease type 1 (ADPKD1).

Thirteen Spanish families with autosomal dominant polycystic kidney disease were studied. In one family the disease did not segregate with polymorphic markers around the PKD1 locus. All subjects over the age of 30 years carrying a mutation at the PKD1 locus showed renal ultrasonographic cysts, but 40% of carriers of the PKD1 mutation younger than 30 years did not have renal cysts. Hypertension was found to be more frequent in those with renal cysts. Recombinants between 16p polymorphic loci and the PKD1 locus are described.

Adult↗
PubMed1992

Small preterm infants (less than or equal to 1500 g) have only a sustained decrease in ventilation in response to hypoxia.

The classic "biphasic" ventilatory response to 15% O2 was previously observed in preterm infants who were large compared with those in the intensive care nursery today. We hypothesized that in the smaller infant (less than or equal to 1500 g) the response might be closer to that of the fetus, with no initial increase in ventilation. Thus, we studied 14 healthy preterm infants less than or equal to 1500 g [birth weight 1200 +/- 63 g (mean +/- SEM); gestational age 29 +/- 0.4 wk; postnatal age 17 +/- 3 d] during rapid eye movement and quiet sleep. Ventilation was measured using a nosepiece and a flow-through system. Sleep states were defined using EEG, electro-oculogram, and body movements. After a control period in 21% O2 (3 min), infants breathed 15% O2 for 5 min. In rapid eye movement sleep, minute ventilation decreased from 0.186 +/- 0.020 (control) to 0.178 +/- 0.021 (30 s), to 0.171 +/- 0.017 (1 min; p = 0.03), to 0.145 +/- 0.016 (3 min; p = 0.002), and to 0.129 +/- 0.011 l.min-1.kg-1 (5 min; p = 0.004). In quiet sleep, it decreased from 0.173 +/- 0.019 (control) to 0.164 +/- 0.019 (30 s), to 0.166 +/- 0.019 (1 min), to 0.148 +/- 0.013 (3 min; p = 0.03), and to 0.146 +/- 0.012 l.min-1.kg-1 (5 min; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1992

Infant mortality, per capita income, and adult illiteracy: an ecological approach.

The ecological association of infant mortality rate (IM) with per capita income (PI) and prevalence of adult illiteracy (AI) has been studied using countries as the unit of analysis. A negative association between IM and PI in 1960 and 1982 has been observed (sample correlation coefficient [r] = -.625 and r = -.729, respectively; P less than .05). A correlation between IM and AI has been found for both men and women (r = .827 and r = .855, respectively; P less than .05). The ecological relative risks were 7.43 for men and 5.82 for women (95% confidence intervals: 5.16-10.71 and 4.36-7.75, respectively). The association of IM and PI shows a slight but not significant improvement between 1960 and 1982. AI can be considered a good predictor of IM in countries.

Bias↗
PubMed1992

The effects of gestational age and labour on the breathing and behaviour response to oxygen and umbilical cord occlusion in the fetal sheep.

We tested the hypothesis that the continuous breathing response to oxygen or oxygen plus umbilical cord occlusion, in the fetal sheep, could be modified by gestational age or labour. We studied 35 chronically instrumented fetal sheep on 84 occasions during late gestation (124 to 141 days), using our window model (Rigatto, 1984). After a resting cycle (1 low-voltage followed by 1 high-voltage electrocortical activity epoch), the fetal lung was distended via an endotracheal tube using mean airway pressure of about 30 cm H2O. Inspired nitrogen, and 100% O2 were given to the fetus during one cycle each. While on 100% O2 the umbilical cord was occluded using a balloon cuff. We found that: (1) the continuous breathing response to 100% O2 occurring in 8% of the experiments at a gestational age less than 130 days, in 25% from 130 to 134 days and in 45% at gestational ages greater than 134 days (P < 0.01); (2) at similar gestational age intervals the breathing responses to umbilical cord occlusion were 67%, 84%, and 100% (P < 0.01); and (3) in the presence of labour, 45% of the experiments responded to O2 with continuous breathing as compared to 23% in the absence of labour (P < 0.01). Cord occlusion did not affect these values. Because the highest PaO2 achieved increased significantly to 128 days but not thereafter it is unlikely that these results can be explained on the basis of an increase in PaO2 alone. We speculate that there is an age related maturation of the inhibition of breathing normally present in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of 21 or 30% O2 plus umbilical cord occlusion on fetal breathing and behavior.

We have shown previously that continuous fetal breathing can be induced by 100% O2 alone or combined with umbilical cord occlusion (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990). To know whether it could also be induced by lower O2 concentrations plus cord occlusion, we studied 9 chronically instrumented fetal sheep (16 experiments) using our window model. After a baseline cycle [1 low voltage + 1 high voltage electrocortical activity (ECoG) epoch] the fetal lung was distended via an endotracheal tube to about 30 cm H2O. Inspired N2 (control) and 21 or 30% O2 were given for one cycle each. While on 21% or 30% O2 the umbilical cord was occluded (balloon cuff). In 10 out of 16 experiments breathing output (% maximum of integral of EMGdi x f) increased after cord occlusion from 80 +/- 48 (N2) to 2871 +/- 641 (SEM; P < 0.01); in 7 of them breathing became continuous. Arterial PO2 increased from 14 +/- 1 (N2) to 33.5 +/- 5 Torr (occlusion; P < 0.01). In the other 6 experiments breathing output decreased from 319 +/- 116 (N2) to 86 +/- 38 (occlusion; P < 0.01) and arterial PO2 changed from 18 +/- 1 (N2) to 22 +/- 5 Torr (occlusion; P = 0.4). Arterial PCO2 increased similarly after occlusion in both groups, those which did respond with increased breathing (to 46 +/- 2 Torr) and those which did not respond (to 48 +/- 3 Torr; P = 0.6). The percent low voltage ECoG and the behavioral score increased after occlusion in the responder group only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗