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M Perez

Publications and source records attributed to M Perez.

At least 163 records · Page 9Linked to original sources

Developmental changes in rat hepatic casein kinases 1 and 2.

Cytosolic histone kinase and casein kinase activities varied considerably in the late fetal and postnatal periods of liver development. Both activities showed a maximum at day 21 of gestation and decreased at birth to values close to those of adult rats. The changes in total casein kinase activity were due to variations of casein kinase 1 and casein kinase 2. Similarly the activities of both the cyclic-AMP-dependent protein (histone) kinase and the cyclic-AMP-independent histone kinase varied during development. Besides the changes in total activity, the affinity of casein kinases 1 and 2 for casein also varied in fetal and postnatal development. The Km values of casein kinase 2 increased from day 18, reached a maximum at day 20 of gestation and then started to decrease until one day after birth. In contrast the Km values of casein kinase 1 decreased from day 18, reached its lowest value at day 21 of gestation and attained values similar to those in the adult at the day of birth. Changes in this parameter were also observed when insulin (3 IU/kg) was administered by intraperitoneal injection to one-day-old rats. The Km values of casein kinase 1 decreased while those of casein kinase 2 increased after administration of this hormone. On the other hand, the Km values for ATP of casein kinases 1 and 2 as well as their apparent molecular masses and sensitivity to heparin and GTP did not significantly change during ontogeny of rat liver.

Aging↗

Low affinity binding sites for 1,4-dihydropyridines in mitochondria and in guinea pig ventricular membranes.

In this paper, we describe the occurrence of both high and low affinity sites for dihydropyridines in crude membrane preparations from guinea pig ventricular tissue. The physiological significance of the low affinity site (apparent dissociation constant = 76 +/- 9 nM) is not currently known; it has, however, a binding capacity which was 300-1000 times that of the high affinity site and was resistant to heat denaturation. The magnitude of the binding to the low affinity site was affected by both the ionic strength of the medium and by the presence of divalent ions. Both unlabeled nitrendipine and nimodipine inhibited [3H]nitrendipine binding at both sites, but verapamil and diltiazem only affected binding at the high affinity site. We also characterized, both kinetically and by equilibrium binding, a low affinity, heat-stable nitrendipine binding site in purified mitochondria. The Bmax for this site was also dependent on ionic strength. This suggests the possibility that the low affinity site in crude membranes is due to mitochondrial contaminants and hence not directly related to voltage-dependent calcium channels.

Animals↗

Toxins that affect voltage-dependent calcium channels.

At this time, there are five potential candidates for calcium channel specific toxins. All five of these toxins appear to affect the function of voltage-dependent calcium channels. Atrotoxin, beta-leptinotarsin-h and maitotoxin activate channels, whereas both taicatoxin and omega-conotoxin are inhibitors. Neither maitotoxin nor omega-conotoxin alters the binding of dihydropyridines to membranes derived from the cells upon which the toxins exert their effects. In contrast, both atrotoxin and taicatoxin inhibit the binding of dihydropyridines to ventricular membranes. It is not currently known whether beta-leptinotarsin-h affects the binding. The effects of maitotoxin and atrotoxin are blocked by dihydropyridines and verapamil. Direct binding studies with radiolabeled toxins have been performed only with omega-conotoxin, and the binding site density for this toxin appears to be at least one order of magnitude greater than the density of dihydropyridine binding sites in synaptosomes. Studies to examine the third and fourth criteria which we have listed (i.e. that the effects are not via a second messenger, or an enzyme activity) have not been reported for either beta-leptinotarsin-h or omega-conotoxin. Atrotoxin and taicatoxin, added outside a patch pipette, have no effects on calcium channels within the patch and are, therefore, probably not affecting calcium channels via a second messenger. Maitotoxin, however, affects the formation of inositol phosphates and, hence, could be affecting the channel indirectly. The fractions containing the toxic components atrotoxin and taicatoxin have no phospholipase or protease activity, and this is presumably true also for omega-conotoxin since it has been purified to homogeneity. Although all of the toxins have the potential to be important tools with which to study calcium channel structure and function, a number of experiments remain to be done in order to establish conclusively that these five toxins bind specifically to the voltage-dependent calcium channel. In conclusion, we would like to briefly mention why so much effort is being devoted to the search for these calcium channel specific toxins. Such a toxin would provide a very valuable tool in the study of calcium channels for a number of reasons. First, the toxin would be another ligand for the channel and, as such, would provide an alternative to organic ligands such as the dihydropyridines which are lipophilic and, in many tissues, have more than one binding site.(ABSTRACT TRUNCATED AT 400 WORDS)

Binding Sites↗

Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants.

The efficacy of the rhesus rotavirus vaccine candidate MMU-18006 was evaluated in a longitudinal double-blind field trial in Caracas, Venezuela. 247 infants aged 1-10 months were studied and followed for up to 1 year (201 completed the 1-year surveillance): 123 received a dose of 10(4) plaque-forming units of the vaccine orally and 124 received placebo. 21 episodes of rotavirus diarrhoea were detected, 16 in the controls and 5 in the vaccines: vaccine efficacy against any rotavirus diarrhoea was thus 68%. In the 1-5-month-old group the vaccine efficacy was 93%; only 1 episode of rotavirus diarrhoea was detected in 68 vaccinees and 15 such illnesses were observed in 65 controls (p less than 0.0001). For the entire study group vaccine efficacy was 100% against the most severe rotavirus diarrhoeal episodes.

Antibodies, Viral↗

[KID syndrome (keratitis-ichthyosis-deafness)].

The KID syndrome is characterized by congenital ichthyosis, vascular keratitis and neurosensorial deafness. We report a 17 year old female patient, the first case of KID syndrome in Spanish literature. Red, dry, scaling skin was present at birth with sparse hair. At the age of six, malar erythema was prominent, with perioral ragades and onset of progressive neurosensory deafness. At the age of ten, vascularizing keratitis developed. At 12, treatment with etretinate failed to improve the ichthyosis. We review the clinical, pathological and analytical features of KID syndrome and discuss its relationship to other ichthyoses.

Adolescent↗

Topography of glycosylation reactions in the rough endoplasmic reticulum membrane.

The translocation of UDP-glucose and GDP-mannose from an external to a luminal compartment has been examined in rat liver vesicles derived from the rough endoplasmic reticulum (RER). RER vesicles with the same topographical orientation as in vivo were incubated with a mixture of [3H]UDP-glucose and UDP-[14C]glucose to demonstrate that the intact sugar nucleotide was translocated into the lumen of the vesicles. The translocation of UDP-glucose was dependent on temperature and was saturable at high concentrations of the sugar nucleotide. The transfer of glucose to endogenous acceptors was dependent on the translocation of UDP-glucose into the lumen of the RER since leaky vesicles resulted in both a decrease in transport and transfer of glucose to endogenous acceptors. Preliminary results suggest that the mechanism of UDP-glucose transport into RER-derived vesicles is via a coupled exchange with luminal UMP. Using the same experimental approach to detect translocation of UDP-glucose into the lumen of RER vesicles, we were unable to detect transport of GDP-mannose. Incubation of leaky vesicles with GDP-mannose resulted in stimulation of the amount of mannose transferred to endogenous acceptors, in marked contrast to that observed for UDP-glucose and UDP-N-acetylglucosamine. These results suggest that whereas UDP-glucose is translocated across the RER membrane in vitro, GDP-mannose is not transported. In addition, these results tentatively suggest that there is asymmetric synthesis of the lipid-linked oligosaccharides within the membrane of the RER.

Animals↗

Translocation of UDP-N-acetylglucosamine into vesicles derived from rat liver rough endoplasmic reticulum and Golgi apparatus.

A mixture of UDP-N-acetylglucosamine labeled with different radioisotopes in the uridine and glucosamine was used to show that the intact sugar nucleotide was translocated across the membrane of vesicles derived from rat liver rough endoplasmic reticulum (RER) and Golgi apparatus. Translocation was dependent on temperature, saturable at high concentrations of sugar nucleotide, and inhibited by treatment of vesicles with proteases, suggesting protein carrier mediated transport. Translocation of UDP-GlcNAc by RER-derived vesicles appeared to be specific since these vesicles were unable to translocate UDP-galactose, in contrast to those derived from the Golgi apparatus. Preliminary results suggest that the mechanism of UDP-GlcNAc translocation into RER-derived vesicles is via a coupled exchange with lumenal nucleoside monophosphate. This is similar to the recently postulated mechanism for translocation of sugar nucleotides into vesicles derived from the Golgi apparatus.

Animals↗

Genetic relatedness among human rotaviruses.

The genetic relatedness of 81 clinical rotavirus isolates to the human rotavirus prototype strains Wa (subgroup 2, serotype 1) and DS-1 (subgroup 1, serotype 2) was examined by RNA hybridization techniques. Labeled single-stranded (+) transcripts of Wa or DS-1 virus were incubated with denatured genomic rotaviral RNAs, and the resulting hybrids were subjected to gel electrophoresis and autoradiography. Nineteen of the specimens contained subgroup 1 rotavirus with a "short" RNA migration pattern. These viruses were found to be closely related to the DS-1 strain and were associated with illness of short duration. The remaining 62 isolates belonged to subgroup 2 and exhibited a "long" RNA migration pattern. Fifty-four of these isolates exhibited significant hybridization with the Wa strain probe. Four isolates yielded multiple hybrid bands with the Wa probe but also possessed at least one gene segment homologous to the DS-1 strain. The remaining four subgroup 2 rotaviruses did not exhibit significant homology in the form of labeled hybrid bands when tested with either the Wa or DS-1 probe. These findings suggest that most clinical rotavirus isolates belong to one of two human rotavirus "families" defined as Wa-like or DS-1-like. Our observations also suggest that reassortment occurs in vivo between rotaviruses belonging to the two human rotavirus "families" and that there are one or more additional families of human rotavirus.

Genes, Viral↗

Cryptosporidiosis in Venezuelan children with acute diarrhea.

Thirteen of 120 Venezuelan children with acute diarrhea were found to be excreting Cryptosporidium oocysts in their stools. This confirms that Cryptosporidium can infect immunocompetent children, and the relatively high frequency found suggests that this protozoan may be an important cause of diarrhea in Venezuela.

Acute Disease↗