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Biomedical subjects

A Ferrer

Publications and source records attributed to A Ferrer.

At least 145 records · Page 8Linked to original sources
PubMed1989

[Diagnosis by DNA analysis in familial isolated growth hormone deficiency type I-A].

We show the autoradiograms of DNA from one child affected of familial isolated growth hormone deficiency type I-A. Restriction endonuclease analysis of DNA isolated from leukocytes was done using 32P-labeled human GH cDNA clone as a probe. DNA analysis using the restriction endonuclease Bam HI revealed that the 3.8 kb restriction fragment, which contain the normal hGH-N gene, was absent. Since these deletions preclude production of any GH-N protein, affected individuals tend to be immunologically intolerant to exogenous GH. The child was homozygote and after treatment with exogenous GH developed a high titre of antibodies to GH and growth arrest. This is the first case of this genetic disorder studied in Spain.

Autoradiography↗
PubMed1989

Isolation and structural characterization of a cDNA encoding Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) catalyses the synthesis of mevalonate, the specific precursor of all isoprenoid compounds present in plants. We have characterized two overlapping cDNA clones that encompass the entire transcription unit of an HMG-CoA reductase gene from Arabidopsis thaliana. The transcription product has an upstream non-coding sequence of 70 nucleotides preceding an open reading frame of 1776 bases and a 3' untranslated region in which two alternative polyadenylation sites have been found. The analysis of the nucleotide sequence reveals that the cDNA encodes a polypeptide of 592 residues with a molecular mass of 63,605 Da. The hydropathy profile of the protein indicates the presence of two highly hydrophobic domains near the N-terminus. A sequence of 407 amino acids corresponding to the C-terminal part of the protein (residues 172-579), which presumably contains the catalytic site, shows a high level of similarity to the region containing the catalytic site of the hamster, human, yeast and Drosophila enzymes. The N-terminal domain contains two putative membrane-spanning regions, in contrast to the enzyme from other organisms which has seven trans-membrane regions. A. thaliana contains two different HMG-CoA reductase genes (HMG1 and HMG2), as estimated by gene cloning and Southern blot analysis. Northern blot analysis reveals a single transcript of 2.4 kb in leaves and seedlings, which presumably corresponds to the expression of the HMG1 gene.

Amino Acid Sequence↗
PubMed1989

Epidemics due to pesticide contamination of food.

Clinical and epidemiological aspects of epidemics of poisoning due to pesticides are reviewed. The 37 cases chosen are divided into four groups on the basis of implication for prevention.

Disease Outbreaks↗
PubMed1988

Pathological spectrum of the lung in cases of violent death: Part I. Lesion classification.

The results are presented of the pathological study of the lungs in 66 cases of violent death observing the more frequent types of lesions and establishing 4 different groups of postlesioned pulmonary condition. 1. Inflammatory alveolar lesions without a diffused interstitial involvement (IAL) including contusions or direct aggressions, lobular pneumonias, or bronchopneumonias with a predominance of intra-alveolar inflammatory exudation. 2. Inflammatory alveolar lesions with a diffuse interstitial involvement (IALW) including generalized affectation of the parenchyma with lesions in the capillary structure of the wall. 3. Edemohemorrhagic lesions (EHL) presenting phenomena of capillary congestion with hematic extravasation and interstitial and intra-alveolar edema, without inflammatory involvement. This is the most numerous group and it can constitute the preliminary stage of any other. 4. Unspecific chronic lesions (UCL) not related to the cause of death, being chronically inflammatory and fibrotic alterations of limited interest in our study. We emphasize the importance of the inflammatory involvement of the alveolar wall in the pathogenia of diffuse alveolar damage (DAD) and the aggravation of pulmonary lesions by capillary structure alteration, direct lesion of alveolar epithelium, presence of macrophages, and liberation of certain intracellular enzymes.

Asphyxia↗
PubMed1988

Pathological spectrum of the lung in cases of violent death: Part II. Clinicopathologic correlation.

The correlation between the type of pathological lesion of the lung and the circumstances which encompass their evolution in 66 cases of violent death have been examined. Pulmonary lesions have been classified into four groups. 1. Inflammatory alveolar lesions without a diffuse interstitial involvement (IAL) which result from direct aggressions in subjects of advanced age. 2. Inflammatory alveolar lesions with a diffuse interstitial affectation (IALW) which are more frequent in younger subjects having a higher defense capacity and with severe lesions requiring admission to an intensive care unit. 3. Edemohemorrhagic lesions (EHL) appearing as a precocious lesion at any age. 4. Unspecific chronic lesions (UCL) previous to the aggression and without any relationship to death. The most obvious feature noted was the frequent occurrence of certain types of acute pulmonary lesions indicative of the rapid and extensive capacity of the lung to react to a lesion agent even when death follows rapidly after the aggression. The scarcity of acute interstitial lesions among the older group can be related to a diminution of biological defense activity leading to a less vigorous response; on the contrary, diffuse lesions of the wall seem to be related to an excess of defense mechanisms, determined more by age, severity of lesion, and type of medical assistance received than by a specific type of aggression.

Adult↗
PubMed1987

Reaction of 5'-p-fluorosulfonylbenzoyladenosine with the catalytic and AMP allosteric sites of microsomal HMG-CoA reductase kinase.

The nucleotide analogue 5-p-fluorosulfonylbenzoyladenosine reacts with rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase kinase, causing a rapid loss of the AMP activation capacity and a slower inactivation of the catalytic activity. The rate constant for loss of AMP activation is eleven times higher (K1 = 0.107 min-1) than the rate constant for inactivation (K2 = 0.0094 min-1). Mg-ATP protects preferentially against inactivation, while Mg-AMP at a low concentration (7.5/0.05 mM) protects preferentially against loss of the AMP activation capacity. Oppositely, Mg-ADP at a low concentration (7.5/0.05 mM) hardly protects against loss of AMP activation capacity. We conclude that microsomal reductase kinase has distinct sites for activation and catalysis.

AMP-Activated Protein Kinases↗
PubMed1987

Affinity labeling of the catalytic and AMP allosteric sites of 3-hydroxy-3-methylglutaryl-coenzyme A reductase kinase by 5'-p-fluorosulfonylbenzoyladenosine.

The nucleotide analogue 5'-p-fluorosulfonylbenzoyladenosine (FSBA) reacts irreversibly with rat liver cytosolic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase kinase, causing a rapid loss of the AMP activation capacity and a slower inactivation of the catalytic activity. The rate constant for loss of AMP activation is about 10 times higher (kappa 1 = 0.112 min-1) than the rate constant of inactivation (kappa 2 = 0.0106 min-1). There is a good correspondence between the time-dependent inactivation of reductase kinase and the time-dependent incorporation of 5'-p-sulfonylbenzoyl[14C]adenosine ([14C]SBA). An average of 1.65 mol of reagent/mol of enzyme subunit is bound when reductase kinase is completely inactivated. The time-dependent incorporation is consistent with the postulate that covalent reaction of 1 mol of SBA/mol of subunit causes complete loss of AMP activation, whereas reaction of another mole of SBA/mol of subunit would lead to total inactivation. Protection against inactivation by the reagent is provided by the addition of Mg2+, AMP, Mg-ATP, or Mg-AMP to the incubation mixtures. In contrast, addition of ATP, 2'-AMP, or 3'-AMP has no effect on the rate constants. Mg-ATP protects preferentially the catalytic site against inactivation, whereas Mg-AMP at low concentration protects preferentially the allosteric site. Mg-ADP affords less protection than Mg-AMP to the allosteric site when both nucleotides are present at a concentration of 50 microM with 7.5 mM Mg2+. Experiments done with [14C]FSBA in the presence of some protectants have shown that a close correlation exists between the pattern of protection observed and the binding of [14C]SBA. The postulate is that there exists a catalytic site and an allosteric site in the reductase kinase subunit and that Mg-AMP is the main allosteric activator of the enzyme.

AMP-Activated Protein Kinases↗
PubMed1987

Bronchial adenocarcinoma presenting as a lingual tonsillar metastasis.

We describe a case of a lingual tonsillar metastasis as the first manifestation of a bronchial adenocarcinoma. Tonsillar metastases infrequently become manifest before the diagnosis of the primary neoplasm. A review of the literature disclosed 89 cases of carcinoma metastasizing to the palatine tonsil, but no one has reported the involvement of the lingual tonsil. Our patient is the first described case of bronchogenic carcinoma with this unusual form of presentation and furthermore is also the first carcinoma metastasizing to the lingual tonsil.

Adult↗
PubMed1987

Allosteric activation of rat liver microsomal [hydroxymethylglutaryl-CoA reductase (NADPH)]kinase by nucleoside phosphates.

Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase kinase activity is enhanced about 5 fold by 2 mM of either AMP or ADP. Activation constants, Ka, for AMP and ADP are 17 microM and 430 microM respectively, showing that AMP is a more potent activator than ADP. This property is expressed by increasing not only the rate of reductase inactivation but also the rate of reductase phosphorylation from [gamma-32P]ATP. GTP can replace ATP as substrate of reductase kinase but GMP and GDP cannot replace AMP as activators. Kinetic studies show that ATP can only act as a substrate. Nucleoside mono or diphosphates and nucleoside triphosphates, thus, appear to bind to different sites on microsomal HMG-CoA reductase kinase. Nucleoside mono or diphosphates act as allosteric activators of reductase kinase. The adenosyl moiety and the unaltered phosphate ester at the 5' position are two essential features of the activator molecule. Phosphorylation of reductase either by microsomal or cytosolic AMP-activated reductase kinase produces an 80% inactivation, with a concomitant incorporation of 0.8 mol of 32P per mol of reductase (Mr 55,000). In both cases exhaustive tryptic digestion of 32P-labeled HMG-CoA reductase, which had been denatured in 2M urea, yields two major phosphopeptides, the phosphoryl group being bound to serine residues.

AMP-Activated Protein Kinases↗
PubMed1985

Activation of rat liver cytosolic 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase by adenosine 5'-monophosphate.

Inactivation of 3-hydroxy-3-methylglutaryl Coenzyme A reductase by reductase kinase and ATP-Mg needs either ADP or 5'-AMP as cofactors. 5'-AMP is a more potent activator of cytosolic reductase kinase than ADP. This capacity is expressed by increasing not only the rate of reductase inactivation, but also the rate of reductase phosphorylation from [gamma-32P]ATP. Activation constants, Ka, for 5'-AMP and ADP are 20 microM and 420 microM respectively. Neither 3'-AMP nor 2'-AMP activate reductase kinase. Other nucleoside monophosphates like UMP, CMP and GMP cannot replace 5'-AMP as activators of reductase kinase.

AMP-Activated Protein Kinases↗
PubMed1984

Phosphorylation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase.

Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase kinase has been purified to apparent homogeneity by a process involving the following steps: solubilization from microsomes and chromatography on Affi-Gel Blue, phosphocellulose, Bio-Gel A 1.5m, and agarose-hexane-ATP. The apparent Mr of the purified enzyme as judged by gel-filtration chromatography is 205,000 and by sodium dodecyl sulfate-gel electrophoresis is 105,000. Immunoprecipitation of homogeneous reductase phosphorylated by reductase kinase and [gamma-32P]ATP produces a unique band containing 32P bound to protein which migrates at the same Rf as the reductase subunit. Incubation of 32P-labeled HMG-CoA reductase with reductase phosphatase results in a time-dependent loss of protein-bound 32P radioactivity, as well as an increase in enzymic activity. Reductase kinase, when incubated with ATP, undergoes autophosphorylation, and a simultaneous increase in its enzymatic activity is observed. Tryptic treatment of immunoprecipitated, 32P-labeled HMG-CoA reductase phosphorylated with reductase kinase produces only one 32P-labeled phosphopeptide with the same Rf as one of the two tryptic phosphopeptides that have been reported in a previous paper. The possible existence of a second microsomal reductase kinase is discussed.

AMP-Activated Protein Kinases↗