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Biomedical subjects

C Hubert

Publications and source records attributed to C Hubert.

At least 55 records · Page 3Linked to original sources

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↗

Hypotensive actions of diltiazem and nitroprusside compared during fentanyl anaesthesia for total hip arthroplasty.

The potential for inducing hypotension during fentanyl anaesthesia by administering either diltiazem (n = 7) or sodium nitroprusside (n = 7) was investigated during total hip arthroplasty. Haemodynamic variables were obtained in the lateral position before, during and after administration of the hypotensive agent. Diltiazem 0.15 mg X kg-1 given as an IV bolus followed by a 12.5 +/- 3 micrograms X kg-1 X min-1 continuous infusion decreased mean arterial pressure (MAP) from 77 +/- 11 mmHg to 63 +/- 16 mmHg (p less than 0.05) while other haemodynamic parameters showed only minor and insignificant changes. Hypotension continued for at least 30 min after the cessation of diltiazem. With sodium nitroprusside MAP decreased immediately from 81 +/- 11 mmHg to 59 +/- 9 mmHg (p less than 0.01) and rapidly returned to its control value after cessation of the infusion. CI and Qs/Qt rose significantly (p less than 0.05) while the systemic vascular resistance index (SVRI) (p less than 0.01) and pulmonary vascular resistance index (PVRI) (p less than 0.05) fell significantly. The haemodynamic profile was significantly different between hypotensive agents for MAP (p less than 0.02), heart rate (HR) (p less than 0.01), SVRI (p less than 0.05), and PVRI (p less than 0.05). HR was lower with diltiazem than with nitroprusside. A bradycardia less than 50 beats/min was observed in five patients in the diltiazem group. MAP, SVRI and PVRI were lower with nitroprusside than with diltiazem. Diltiazem can induce and maintain moderate hypotension without tachycardia and decreased cardiac output in humans during fentanyl anaesthesia but the modulation of the level of arterial pressure and the depression of atrioventricular conduction are unpredictable.

Aged↗

[Pulmonary digital subtraction angiography. A comparative study of 2 technics. Electrocardiographic servo-assistance versus 3 images per second].

A prospective study in 60 consecutive patients evaluated gain in quality of image using ECG servo-assistance during pulmonary digital subtraction angiography (PDSA). Two groups of 30 comparable patients were randomly allocated to examination with ECG servo-assistance or three images per second technique. Criteria for assessment of quality of image were defined and used to compare results. No significant difference were noted and ECG servo-assistance failed to improve images during PDSA.

Adolescent↗

[Spinal anesthesia with bupivacaine in lower urologic surgery. Our experience apropos of 500 cases].

Rachianesthesia was used for 500 lower urinary tract operations, including 50 repeat procedures, the anesthetic employed being bupivacaine. Patients were frequently hypertensive and presented cardiopathies, usually ischemic in origin. The surgical procedure generally involved transurethral prostate resection for adenoma or carcinoma, or endoscopic resection of a bladder tumor, and all patients received preventive heparin therapy using Kakkar's method. Induction of anesthesia occurs between 30 seconds and one minute after completing the injection a procedure lasting 2 to 5 minutes. Full anesthesia is obtained after 2 to 3 minutes, and is maintained during the mean operation period of 69 +/- 32 minutes by regular intraspinal injections of anesthetic. Results were perfect in 425 cases, 48 patients required additional sedatives, 23 a potent analgesic and 4 a general anesthetic after an operating time extending beyond 100 minutes heart rate remained fairly regular while diminishing slightly in frequency (an average of 4 beats/min). The fall in blood pressure was globally moderate (296 patients) and was unaltered in 204 cases. Hemodynamic modifications lasted for 3 à 4 minutes only and were corrected by appropriate therapy. Postoperative complications were mainly of the headache type (26 cases: 5%), but three patients developed angina from a coronary ischemic accident. Myocardial infarction was not observed, and no particularly incidents were reported in the 32 patients requiring repeat rachianesthesia. The simple execution and efficacy of this mode of anesthesia is emphasized, an additional need for general anesthesia being a rare event. The compound is well tolerated, hemodynamic modifications are moderate and neurological sequelae lacking. Rachianesthesia with bupivacaine appears to be among the methods of choice for lower urinary tract surgery.

Adolescent↗

Plasma human chorionic somatomammotropin deficiency in a normal pregnancy is the consequence of low concentration of messenger RNA coding for human chorionic somatomammotropin.

Human chorionic somatomammotropin (hCS) is important in the hormonal monitoring of human pregnancies. Presented is the case of a clinically normal pregnancy in which a very low plasma level of hCS was detected. The concentration of messenger ribonucleic acid (mRNA) coding for hCS was evaluated to determine the level on which the deficiency occurred.

Adult↗

Effect of vitamin C supplements on cell-mediated immunity in old people.

Both ageing and vitamin C (VC) deficiency result in immune defect. Since low serum and tissue levels of VC are found in the elderly, we have in a placebo-controlled study, tested the effect of VC supplements (500 mg/day i.m. for 1 month) on various immune parameters. Indeed, VC enhances the proliferative response of T lymphocytes in vitro, and the tuberculin skin hypersensitivity in vivo. Neither the serum concentrations of IgA, IgG and IgM, nor the proportion of E-rosette-forming cells were modified. No significant change was observed in the placebo-treated group.

Aged↗

Biologic activity and quantification of messenger RNA coding for human chorionic somatomammotropin in normal and intrauterine growth--retarded pregnancies.

Total ribonucleic acid (RNA) from human placentas obtained from normal and intrauterine growth--retarded (IUGR) pregnancies was translated in a reticulocyte cell--free system. Synthesis of human chorionic somatomammotropin (hCS) was estimated as a ratio of specific immunoprecipitated protein over total newly synthesized proteins. There is no significant difference between in vitro hCS synthesis directed by placental RNA from normal and IUGR pregnancies. Measurements of messenger RNA sequences coding for hCS, with a hCS complementary DNA probe, indicated that the hCS messenger RNA (mRNA) concentrations were similar for both groups. Low plasma hCS levels in pregnancies associated with growth-retarded fetuses can be explained by their significantly lower placental weights which correlate with their total RNA content. The total capacity of in vitro hCS production per placenta is significantly lower in this type of abnormal pregnancy. There is a good parallelism between the amount of hCS mRNA, its biologic activity tested in a cell-free system, and the secretion of hCS in the maternal circulation. These data suggest that there is no basic intracellular disturbance in hCS synthesis in placentas from fetal growth--retarded pregnancies.

Female↗

A five-generation family with sacral agenesis and spina bifida: possible similarities with the mouse T-locus.

In man, a malformation that recalls some of the defects associated with T/t mutants in the mouse is sacral agenesis. We report on a family with a high incidence of sacral malformation, ranging from a complete absence of the sacrum (SA), with or without spina bifida aperta, to a spina bifida occulta (SBO) that could only be detected by x-ray. The condition appeared in a man with four children who were all affect, and thereafter, to varying degrees, in 17 of his 28 descendants. Segregation analysis has been performed in this family, using the Elston and Stewart transmission probability model [1971]. The two traits (SA and SBO) were first studied separated and then together. A fully penetrant major dominant gene is show to cause SA. When the phenotypes SA and SBO are considered together, Mendelian transmission is rejected. This could be explained genetically by two alternative hypotheses: genetic heterogeneity or a dominant major gene transmitted in excess by heterozygotes (tau Aa A = 0.896), suggesting a segregation distortion property of an allele at a T-like locus.

Adult↗

Distribution, quantification and biological activity of messenger RNA coding for human chorionic somatomammotropin during normal pregnancy.

Synthesis of hCS by RNA fractions from human placentas obtained at different stages of pregnancy was estimated either by immunological or electrophoretical methods in wheat-germ and reticulocyte cell-free systems. hCS synthesis is preferentially associated with polyribosomes bound to the membrane of the endoplasmic reticulum, as is assumed for a secreted protein. In both translational systems we determined only one precursor form of this hormone of a molecular weight near 24 000. Full-term placentas synthesize hCS as the major protein. This conveniently allowed us to isolate the messenger RNA coding for the hormone and to synthesize a specific hCS complementary DNA which we used as a probe for quantifying sequences of RNA coding for hCS during pregnancy. In placentas from first-trimester pregnancy, the concentration of hCS mRNA was 4 times less than in the full-term organs, and the hCS synthesis per microgram of RNA added into the translational medium was diminished in the same order of magnitude. In placentas from second-trimester pregnancy, the concentration of hCS mRNA was similar to that obtained at term, and in vitro the hCS synthesis per microgram of translated RNA was also similar to that observed at the end of pregnancy. However, the hCS mRNA content per placenta from mid-term pregnancy was much lower than from full-term gestation. We established a good parallelism, as pregnancy progressed, between the hCS mRNA content, its capacity of hCS synthesis in vitro and the maternal plasma hCS level, indicating that hCS production is controlled essentially by the biological active mass of the placenta.

DNA↗

Time differential perturbed angular correlation (TDPAC) studies of the 133Ba ion uptake in bone crystals.

TDPAC measurements of the 356-81 keV gamma-ray cascade resulting from electron capture decay of 133Ba have been performed at room temperature on BaCl2 (aqueous solution and polycrystalline powder), and on samples where the 133Ba nucleus is bound to bone powder, and also to synthesised hydroxylapatite, all after absorption in vitro. As expected, the angular correlation is not perturbed in the solution. However, in the polycrystalline chloride the time dependence of the anisotropy of the cascade of 133Cs nuclide indicates that the decaying nucleus undergoes electric interactions due to different electric field gradients acting at the site of the nucleus. In 133Ba-bone powder the results show a static quadrupolar interaction differing with the absorption contact time during sample preparation, indicating that depth of 133Ba ion fixation in the bone crystal is dependent on this contact time. These results seem to be confirmed by the TDPAC measurements performed on 133Ba-hydroxylapatite samples where the contact times for absorption of active-ion 133Ba and hydroxylapatite in suspension were very different.

Animals↗

Early biochemical events associated with lymphocyte activation in ageing. I. Evidence that Ca2+ dependent processes induced by PHA are impaired.

The requirement for Ca2+, a divalent ion which plays a fundamental role in cell activation, has been analysed in cultures of PHA-stimulated human peripheral blood lymphocytes (PHA-PBL) from adult (range: 20-35 years) and old (over 70 years) subjects. For this purpose, increasing concentrations of Ca2+ chelators (EGTA and EDTA) were added to cultures in order to compare the effect of progressive extracellular Ca2+ (Ca2+EC) depletion on [3H]-Tdr incorporation by PHA-PBL. Kinetic analysis showed that Ca2+EC requirement was restricted to the first 24 h after culture initiation. At optimal doses of PHA, the PHA-PBL from old subjects were more sensitive than those from adult subjects to increasing concentrations of both chelators. They also required larger amounts of Ca2+ supplements to restore their normal response after total inhibition by EGTA. Furthermore, the PHA-PBL from the elderly were hypersensitive to verapamil (Isoptin), a drug which instigates a reversible inhibition of Ca2+-dependent processes associated with lymphocyte transformation, by a quite similar reaction to that induced by chelators. We conclude that the Ca2+-dependent processes in lymphocyte activation are impaired with ageing. Following further experiments and recent work suggesting that lymphocytes need more than one signal to proliferate, the authors speculate on a deficiency of a late activation signal requiring cell-cell interactions in the elderly.

Adult↗