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Y Nordmann

Publications and source records attributed to Y Nordmann.

At least 127 records · Page 7Linked to original sources
PubMed1984

Recurrence risk estimation of acute intermittent porphyria based on analysis of porphobilinogen deaminase activity: a Bayesian approach.

Red cell porphobilinogen deaminase is known to be an indicator of the carrier state for acute intermittent porphyria (AIP). This enzyme was assayed in three groups of individuals at least 15 years old: 105 affected individuals or obligate carriers, 234 unaffected first-degree relatives of patients, and 217 unrelated control persons. Analysis of the distribution of the control enzyme activities suggested presence of three commingled distributions. Also, the overlap between carrier-group and control-group values must be taken into account for genetic counseling of relatives whose enzyme activity lies within the overlap. A Bayesian approach is proposed to derive risks for these individuals, using the observed carrier and control distributions. The method is illustrated by deriving risks for a family from our sample.

Adolescent↗
PubMed1984

Effects of succinylacetone on dimethylsulfoxide-mediated induction of heme pathway enzymes in mouse friend virus-transformed erythroleukemia cells.

Heme has been reported to exert a control over its own biosynthesis and to affect the erythroid differentiation process at different sites. In this study, succinylacetone, a powerful inhibitor of delta-aminolevulinic acid dehydrase was used to block heme synthesis and to study the effects of heme depletion on the dimethylsulfoxide (DMSO)-mediated induction of the heme pathway enzymes in Friend virus-transformed erythroleukemia cells. The presence of succinylacetone in the medium during the DMSO treatment (1) potentiates the induction of delta-aminolevulinic acid synthetase (the first enzyme of the pathway) and this effect is reversed by the addition of exogenous hemin; (2) does not affect the induction of delta-aminolevulinic acid dehydrase (the second enzyme); (3) prevents the induction of porphobilinogen deaminase (the third enzyme), since no increase could be detected in either the enzyme activity or the immunoreactive protein and this effect could not be reversed by the addition of exogenous hemin; (4) does not affect the induction of ferrochelatase. The possible role of heme or of intermediate metabolites of the pathway on the induction of these enzymes during the erythroid differentiation process is discussed.

5-Aminolevulinate Synthetase↗
PubMed1984

Isolation and identification of a cDNA clone coding for rat uroporphyrinogen decarboxylase.

We have cloned and identified a DNA sequence complementary to the mRNA of uroporphyrinogen decarboxylase ( UroDCase ) from rat. This mRNA is a minor species (0.1%) of the total mRNA from anemic rat spleen. Poly(A)+ mRNA was enriched for UroDCase mRNA to 20% purity by a very efficient procedure involving two successive steps of preparative gel electrophoresis under various denaturing conditions. cDNA prepared from partially purified UroDCase mRNA (1% purity) was cloned in the Pst I site of pBR322 by using the homopolymeric G-C tailing method. Primary screening of 500 clones from this cDNA library was performed with a cDNA probe complementary to highly purified mRNA for UroDCase (20% purity) and UroDCase cDNA clones were finally identified by hybrid-selected translation. The rat cDNA clones obtained hybridize to human UroDCase mRNA. This will permit the isolation of the corresponding human gene and molecular analysis of porphyria cutanea tarda, the commonest type of porphyria.

Animals↗
PubMed1984

Molecular cloning of a cDNA sequence complementary to porphobilinogen deaminase mRNA from rat.

A cDNA clone containing sequences complementary to the mRNA coding for anemic rat spleen porphobilinogen deaminase (EC 4.3.1.8) has been isolated. A cDNA library was prepared from partially purified mRNA (1% purity). This library was then screened by colony hybridization, using a cDNA probe derived from porphobilinogen deaminase mRNA further enriched (10-20% purity) by gel electrophoresis in the presence of methylmercury hydroxide. Colonies hybridizing with the probe were analyzed by hybrid-selected translation using anemic rat spleen mRNA. Four recombinant plasmids containing porphobilinogen deaminase cDNA sequences were identified by specific immunoprecipitation of the translational product from hybrid-selected mRNA. Porphobilinogen deaminase mRNA was shown to contain 1800 bases by blot hybridization analysis. The cloned cDNA sequence consists of 1500 bases. Hybridization analysis of poly(A)+ RNA from uninduced and induced mouse erythroleukemic cells indicated that induction to erythroid differentiation by dimethyl sulfoxide results in a 10-fold increase of porphobilinogen deaminase mRNA. The rat cDNA clones hybridize to the corresponding sequences encoding human porphobilinogen deaminase. This property will be useful for isolation of human gene(s) and further characterization of the molecular lesion(s) responsible for acute intermittent porphyria.

Ammonia-Lyases↗
PubMed1984

Assignment of the human gene for delta aminolevulinate dehydrase to chromosome 9 by somatic cell hybridization and specific enzyme immunoassay.

A non-competitive enzyme immunoassay specific for delta aminolevulinate dehydrase has been devised and applied to rodent-human hybrid cell lines. Two different conditions have been used, one specific for the human enzyme and the other indicative of both rodent and human enzymes. The ratio of the values obtained under the two conditions was used to discriminate between positive and negative clones. By this method the gene for ALA dehydrase has been assigned to chromosome 9.

Animals↗
PubMed1984

Enzymatic and immunological studies of uroporphyrinogen decarboxylase in familial porphyria cutanea tarda and hepatoerythropoietic porphyria.

Uroporphyrinogen decarboxylase activity was measured in hemoglobin-free lysates from two patients with hepatoerythropoietic porphyria (HEP) and from 12 unrelated patients with familial porphyria cutanea tarda (PCT). In HEP patients, enzyme activities were 5% of normal, and familial studies clearly confirmed that patients with HEP are cases of homozygous PCT. Immunoreactive uroporphyrinogen decarboxylase was measured by developing a direct and noncompetitive enzyme immunoassay (EIA). For the 12 familial PCT patients, we found an immunoreactive protein decreased (51%) to the same extent as the catalytic activity (48%) [cross-reactive immunological material ( CRIM ) negative]. The children from the HEP family were also CRIM negative, contrasting with another HEP family previously described as CRIM positive; our data support the hypothesis of a heterogeneity in familial uroporphyrinogen decarboxylase deficiency.

Carboxy-Lyases↗
PubMed1983

Study of anaesthetic agents for their ability to elicit porphyrin biosynthesis in chick embryo liver.

Effects of some anaesthetic drugs on the activity of delta-aminolevulinate synthetase and on the formation of porphyrins and cytochrome P-450 were studied in 18-day-old chick embryo livers in ovo. The drugs were either tested alone or with a small dose of 1,4-dihydro-3,5-dicarbethoxycollidine, which reproduces in the embryo liver a partial block in the heme biosynthesis pathway similar to that found in cells of human patients with porphyrias. Two series of local anaesthetics were tested: procaine and its derivatives (proxymetacaine, oxybuprocaine, butacaine and tetracaine) had no (or very slight) porphyrogenic effects. In contrast, lidocaine and its derivatives (bupivacaine, mepivacaine, etidocaine, pyrrocaine and prilocaine) were found to induce delta-aminolevulinate synthetase and to cause accumulation of porphyrins and cytochrome P-450. Some other drugs used in anaesthesiology were tested: fentanyl, morphine, sodium oxybate, pancuronium, pethidine and phenoperidine were found to be non-porphyrogenic; alcuronium was a slight inducer. It is suggested that the inducing drugs should be avoided in patients with hepatic porphyrias.

Anesthetics↗
PubMed1983

Harderoporphyria: a variant hereditary coproporphyria.

Three siblings with intense jaundice and hemolytic anemia at birth were found to excrete a high level of coproporphyrin in their urine and feces; the pattern of fecal porphyrin excretion was atypical for hereditary coproporphyria because the major porphyrin was harderoporphyrin (greater than 60%; normal value is less than 20%). The lymphocyte coproporphyrinogen III oxidase activity of each patient was 10% of control values, which suggests a homozygous state. Both parents showed only mild abnormalities in porphyrin excretion and lymphocyte coproporphyrinogen III oxidase activity decreased to 50% of normal values, as is expected in heterozygous cases of hereditary coproporphyria. Kinetic parameters of coproporphyrinogen III oxidase from these patients were clearly modified, with a Michaelis constant 15-20-fold higher than normal values when using coproporphyrinogen or harderoporphyrinogen as substrates. Maximal velocity was half the normal value, and we also observed a marked sensitivity to thermal denaturation. The possibility that a mutation affecting the enzyme on the active center which is specifically involved in the second decarboxylation (from harderoporphyrinogen to protoporphyrinogen) was eliminated by experiments on rat liver that showed that coproporphyrinogen and harderoporphyrinogen were metabolized at the same active center. The pattern of porphyrin excretion and the coproporphyrinogen oxidase from the three patients exhibited abnormalities that were different from the abnormalities found in another recently described homozygous case of hereditary coproporphyria. We suggest naming this variant of coproporphyrinogen oxidase defect "harderoporphyria."

Animals↗
PubMed1983

Coproporphyrin in urine of newborns with meconium aspiration syndrome.

We evaluated coproporphyrin in the first urine passed by newborn infants with and without meconium aspiration, by spectrophotometric analysis and thin-layer and "high-performance" liquid chromatography. Urines of newborn infants without meconium aspiration contained only very small quantities of coproporphyrin, detected, after partial purification, by "high-performance" liquid chromatography. Urines of newborn infants with meconium aspiration contained large quantities of coproporphyrin, identified by all three techniques. Urinary coproporphyrin as measured spectrophotometrically correlates well with the "urinary meconium index," and the method is simple, rapid, and reliable, even for samples containing hemoglobin.

Chromatography, High Pressure Liquid↗
PubMed1982

Assignment of human uroporphyrinogen I synthase locus to region 11qter by gene dosage effect.

Recently Meisler et al. (1980) reported the results of mouse/human somatic cell hybrid studies which indicated that the locus for human uroporphyrinogen I synthase (UPS) (EC 4.3.1.8) maps to chromosome 11. To evaluate further this assignment we have children with a trisomy of the region 11qter. We confirm the results of Meisler et al. (1980) and demonstrate that uroporphyrinogen I synthase activity is increased by a factor of 1.5 in trisomy 11qter. In erythrocytes of one child with a trisomy 11p, the expression of this enzyme was normal.

Adult↗
PubMed1982

Coproporphyrinogen III oxidase assay.

An assay for coproporphyrinogen oxidase activity is described which uses a [14C]-coproporphyrinogen substrate with product isolation by methylation, extraction, and thin layer chromatography. This method affords high sensitivity, since a high specific activity of the substrate and good reproducibility due to the incorporation of an internal standard can be obtained. The activity in rat liver and human lymphocytes was found to be 140 nmol protoporphyrin/h/g of liver and 483 pmol protoporphyrin/h/mg of lymphocyte protein, respectively.

Animals↗
PubMed1982

[Myoglobinuria following anesthesia (author's transl)].

In a 11 1/2 year-old boy, acute myolysis with myoglobinuria followed anesthesia and had a favourable outcome. Biological signs of myolysis, without clinical symptoms seem to be frequent after Halothane-succinylcholine anesthesia. They are even more frequent in children, especially when succinylcholine is repeatedly given during Halothane anesthesia. Patient clinical symptoms (visible myoglobinuria, pain and/or paralysis) are rare and occur chiefly in children with chronic muscular disease, in whom they may be the presenting symptoms.

Anesthesia, General↗
PubMed1981

[Familial and sporadic porphyria cutanea symptomatica (author's transl)].

The measurement of erythrocyte uroporphyrinogen decarboxylase is an easy method to divide porphyria cutanea symptomatica into two different types: (1) a familial type in which erythrocyte urodecarboxylase activity is reduced by about 50% in the patient and in apparently healthy members of his family, the inheritance pattern being consistent with an autosomal dominant trait; and (2) a more widespread sporadic type, with normal erythrocyte urodecarboxylase activity. In the familial type, the enzyme deficiency was found to be present in all tissues examined, whereas in the sporadic type it appears to be restricted to the liver.

Humans↗