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C Hubert

Publications and source records attributed to C Hubert.

At least 19 recordsLinked to original sources
PubMed1992

Functional study of the germinal angiotensin I-converting enzyme promoter.

Polymerase chain amplification experiments indicate that the germinal specific promoter of the angiotensin I-converting enzyme (ACE) is completely extinguished in somatic tissues. Despite this very strict specificity of expression, the germinal ACE promoter is active in transient transfection experiments in two somatic cell lines and one cell line of germinal origin. The analysis of the promoter shows the existence two regulatory elements within the first 350 bp: a proximal positive element and a distal negative element.

Animals↗
PubMed1991

Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene.

Overlapping genomic clones containing the entire sequence of the human angiotensin I-converting enzyme (ACE) gene were isolated from a lamda phage human DNA library. This gene spans 21 kilobases (kb) and comprises 26 exons, ranging in size from 88 to 481 base pairs. Intron-exon boundaries were sequenced and the relative positions of the exons were mapped. The two different mRNAs transcribed from the ACE gene were assigned to their respective exons. The large endothelial type ACE mRNA (4.3 kb long) is transcribed from exon 1 to exon 26, excluding exon 13. The 3-kb long testicular ACE mRNA is transcribed from exon 13 to exon 26. Exon 13 encodes for the 67 amino acids of the NH2-terminal region of the testicular ACE, whereas downstream exons encode a sequence common to both isozymes. The gene duplication suggested by the internal homology of the endothelial ACE mRNA is now confirmed by the presence of two homologous clusters of eight exons (exons 4-11 and exons 17-24) having similar sizes and codon phases at exon-intron boundaries. The presence of two alternate promoters was investigated by ribonuclease protection assays. The different 5' ends of the two ACE transcripts revealed a promoter for the endothelial ACE mRNA in the 5'-flanking region of the first exon and a promoter for the testicular ACE mRNA situated in intron 12.

Bacteriophage lambda↗
PubMed1990

An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval.

Adult↗
PubMed1990

The angiotensin I-converting enzyme (kininase II): progress in molecular and genetic structure.

The complete amino acid sequence of the human angiotensin I-converting enzyme (ACE) has been determined by protein sequencing of the purified kidney enzyme and cDNA cloning in endothelial cell libraries. The ACE molecule comprises 1,306 amino acids. It possesses a signal peptide of 29 residues cleaved off during maturation. The enzyme is most likely anchored to the plasma membrane by a short transmembrane domain situated near the carboxy-terminal extremity. Interestingly, the molecule presents a high degree of internal homology between two large peptidic domains. Each of these domains contains short sequences identical to zinc binding and active site sequences of other zinc metallopeptidases and therefore bears a putative active site. However, earlier experiments indicate only one zinc atom bound per molecule of ACE. Competitive inhibitors seem to interact with a unique class of high-affinity binding site. These observations may suggest that, despite the duplicated structure of the enzyme, there is only one functional active site per molecule of ACE. The respective role of the two homologous domains in this active site remains to be determined. A single gene coding for ACE is present in humans, transcribed as a 4.3-kilobase mRNA species in endothelial cells. In other studies, evidence for a genetic polymorphism in plasma ACE levels has been obtained by analyzing a large group of "healthy" nuclear families. A familial association of plasma ACE levels was observed. A major gene effect can possibly explain part of the interindividual variability observed in this enzyme.

Amino Acid Sequence↗
PubMed1989

The testicular transcript of the angiotensin I-converting enzyme encodes for the ancestral, non-duplicated form of the enzyme.

The endothelial angiotensin I-converting enzyme (ACE) is organized in two large homologous domains, each bearing a putative active site. However, only one of these sites is probably involved in catalyzing the conversion of angiotensin I into angiotensin II. The testicular form of ACE is equally active, encoded by the same gene, but translated from a shorter mRNA. Molecular cloning of the human testicular ACE cDNA indicates that the mRNA codes for 732 residues (vs 1306 in endothelium). The testicular transcript corresponds to the 3' half of the endothelial transcript and encodes one of the two homologous domains of endothelial ACE, preceded by a short specific sequence. This 5' specific sequence contains 228 nucleotides and encodes 67 amino acids, including the putative signal peptide followed by a serine/threonine-enriched region, presumably glycosylated. The testicular transcript corresponds to the ancestral, non-duplicated form of the ACE gene. Since the carboxyl-terminal domain of the endothelial ACE is expressed in the testicular enzyme, it is likely that it bears the active site in both forms.

Amino Acid Sequence↗
PubMed1989

Computed tomography of retained abdominal sponges and towels.

The diagnosis of retained sponges and towels a year or more after surgery is often very difficult. We describe the computed tomographic (CT) findings in 4 patients with this complication; 2 cases of retained sponges and 2 cases of retained towels. While the CT appearance of the retained sponges was not specific, the particular appearance of the retained towels had not been previously described. This appearance is characteristic enough to suggest the correct diagnosis before reoperation.

Abdomen↗
PubMed1989

The angiotensin converting enzyme in the kidney.

Immunohistochemical studies and experiments with microdissected nephron segments indicate that the angiotensin I converting enzyme (ACE) in the kidney is expressed in the vascular endothelial cells of the renal vessels and in the epithelial cells of the proximal convoluted tubule and the pars recta. Angiotensin converting enzyme is a membrane-bound zinc metallopeptidase and the primary structure has recently been determined by protein sequencing and molecular cloning. It is probably anchored to the cell membrane by a single, short, transmembrane domain located near the carboxy-terminal extremity. The larger, externally situated, amino-terminal part of the molecule is organized in two large, highly homologous domains, each with a putative active site. The function of the endothelial enzyme in the renal vessels is primarily related to angiotensin II (Ang II) formation. However, its level of expression in renal vessels, especially at the glomerular level, appears to be very low in the adult human kidney, and there is evidence that the conversion of angiotensin I (Ang I) may be a rate-limiting step in Ang II formation in the kidney. The vascular enzyme may also contribute to the inactivation of kinins in the peritubular circulation. In the epithelial cells of the proximal tubule, ACE is present in both the brush border and the basolateral membrane. Although the basolateral enzyme may be involved in Ang II formation in the peritubular interstitium, the function of the enzyme on the brush border is unknown. The effects of ACE inhibitors on renal function are primarily, if not exclusively, related to Ang II suppression and perhaps kinin potentiation in the renal circulation.

Endothelium, Vascular↗
PubMed1989

The peculiar characteristics of the amino acid sequence of angiotensin I-converting enzyme, as determined by cDNA cloning of the human endothelial enzyme.

The angiotensin-I converting enzyme (ACE) is a membrane bound zinc metallopeptidase of the vascular endothelial cell. Recently, the complete amino-acid sequence of human ACE has been determined by protein sequencing and cDNA cloning in endothelial cell libraries. The ACE is encoded from a 4.3 kb transcript and comprises 1,306 amino acids. The molecule comprises a signal peptide of 29 residues cleaved off during maturation. It is most likely anchored by a short transmembrane domain situated near the carboxyterminal extremity. Interestingly, the molecule presents a high degree of internal homology between two large peptidic domains. Each of these domains contains short sequences identical to zinc binding and active site sequences of other zinc metallopeptidases and therefore bears a putative active site. The ACE gene results probably from duplication and fusion of a more ancestral gene, coding for a putative nonduplicated enzyme. However, despite the duplicated structure of ACE, it has been reported that there is only one zinc atom bound per molecule. Competitive inhibitors seem to interact with a unique high affinity binding site. Therefore, there is only one active site in ACE whose location remains to be determined.

Amino Acid Sequence↗
PubMed1989

[Post-transfusion cytomegalovirus infection in premature infants weighing less than 1,500 g].

The incidence of cytomegalovirus (CMV) infection among 107 low birth weight transfused infants (birth weight less than or equal to 1,500 g) admitted to an intensive care nursery over an 18 month period was evaluated. The diagnosis of CMV infection was based on specific serologic tests (presence of IgM, increased IgG by ELISA technic) and identification of the virus in the urine. During the first 8 months, the infants received untested blood and CMV disease occurred in 8 infants out of 44 (18.2%). During the following 10 months, all transfusions performed in 63 infants were supposed to be CMV negative. However, 32 infants received untested blood due to emergency, and 5 of them developed a CMV infection (15.6%). Finally, only 31 infants received CMV negative blood without any case of CMV infection. These data clearly demonstrate that, considering the severity of the CMV disease in the premature infants, transfusions should be performed with CMV negative blood products.

Cytomegalovirus↗
PubMed1988

Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning.

The amino-terminal amino acid sequence and several internal peptide sequences of angiotensin I-converting enzyme (ACE; peptidyl-dipeptidase A, kininase II; EC 3.4.15.1) purified from human kidney were used to design oligonucleotide probes. The nucleotide sequence of ACE mRNA was determined by molecular cloning of the DNA complementary to the human vascular endothelial cell ACE mRNA. The complete amino acid sequence deduced from the cDNA contains 1306 residues, beginning with a signal peptide of 29 amino acids. A highly hydrophobic sequence located near the carboxyl-terminal extremity of the molecule most likely constitutes the anchor to the plasma membrane. The sequence of ACE reveals a high degree of internal homology between two large domains, suggesting that the molecule resulted from a gene duplication. Each of these two domains contains short amino acid sequences identical to those located around critical residues of the active site of other metallopeptidases (thermolysin, neutral endopeptidase, and collagenase) and therefore bears a putative active site. Since earlier experiments suggested that a single Zn atom was bound per molecule of ACE, only one of the two domains should be catalytically active. The results of genomic DNA analysis with the cDNA probe are consistent with the presence of a single gene for ACE in the haploid human genome. Whereas the ACE gene is transcribed as a 4.3-kilobase mRNA in vascular endothelial cells, a 3.0-kilobase transcript was detected in the testis, where a shorter form of ACE is synthesized.

Amino Acid Sequence↗