Biomedical subjects
Publications and source records attributed to F Hervé.
The occurrence in a previously healthy infant of sudden febrile encephalopathy with shock and metabolic acidosis associated with liver and renal failure and bloody watery diarrhea has been reported by several authors in recent years. We report the same association in a 3 1/2 month-old infant. We discuss the similarities between this clinical picture and malignant hyperthermia and Reye syndrome.
Rat alpha-foetoprotein (alpha-FP) strongly binds the drugs warfarin and phenylbutazone, as does albumin; however, the binding sites for the two drugs seemed to be different. This possibility and the specificity of this/these drug-binding site(s) of rat alpha-FP were investigated by competitive protein-binding experiments with a variety of drugs, representing different pharmacological groups, and biomolecules that are strongly bound by the foetal protein and that are suspected to play a specific role during foetal development. The binding mechanisms were further investigated by using comparisons between computer-derived theoretical displacement curves and experimental points in order to distinguish different possible binding models. The results indicate: that warfarin and phenylbutazone are bound at two distinct sites on rat alpha-FP and that a negative modulatory effect is exerted between the two sites; that the degree of specificity of these two drug-binding sites is different, since the warfarin-binding site appears to be specific for the binding of coumarinic and anthranilic drugs whereas that for phenylbutazone is able to bind substances of very varied chemical structure and is more hydrophobic; that the phenylbutazone-binding site is the site that binds oestrogens that thyroid hormones and, probably, fatty acids and bilirubin are bound at (an)other site(s) but exert negative modulatory effects on phenylbutazone binding. The nature of the different binding areas of rat alpha-FP is compared with that of those already proposed for albumin. The potential risks of toxicity of such interactions between drugs and/or biomolecules on foetal development are also discussed.
One should henceforth systematically search for hypertyrosinemia which, too often, goes unrecognized for years, in patients presenting chronic keratitis associated with palmar and plantar hyperkeratosis. As a matter of fact, this highly crippling disease may be cured with an appropriate diet and the diagnosis, once suspected, is easily confirmed by simple investigations.
The authors report the cases of two unrelated children 16 and 5 years of age respectively, affected with hypertyrosinaemia type II. This condition is characterized by palmo-plantar hyperkeratosis associated with a herpetiform keratitis. The diagnosis is based on the finding of hypertyrosinaemia and hypertyrosyluria, and may be confirmed by their biopsy findings of a cytoplasmic tyrosine amino-transferase deficiency. It is a hereditary autosomal recessive disease. A low phenylalanine and tyrosine diet produced a spectacular improvement but the ocular complications could have been avoided by an earlier diagnosis.
Macrodystrophia lipomatosa is the hypertrophy of a limb or of a limb-segment due to fatty infiltration. X-ray examination of the soft tissues which reveals the presence of fat, most often allows the easy distinction of this disorder from other causes of localized hypertrophy.
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As part of an investigation into whether alpha 1-foetoprotein (alpha 1-FP) plays the same transport role in foetal serum as albumin does in the adult, the binding properties of both proteins were compared with respect to the binding of a series of compounds known to be bound by albumin's specific drug-binding sites. The binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid by rat alpha 1-FP and serum albumin was studied by equilibrium dialysis at 4 degrees C. Rat alpha 1-FP was shown to have neither albumin's high-affinity site II (diazepam as marker) nor its site III (digitoxin and cholic acid as markers). High-affinity binding by alpha 1-FP was found for the specific markers (warfarin, phenylbutazone, azapropazone) of albumin's drug-binding site I. However, instead of albumin's one high-affinity site/molecule, a mean value of 0.5 site/molecule was obtained with rat alpha 1-FP. Charcoal treatment at neutral pH of rat serum albumin did not affect its measured binding properties, but treatment of the alpha 1-FP led to an increased affinity for warfarin, phenylbutazone and azapropazone without a change in the measured number of sites, indicating competition for binding at this site by (an) endogenous ligand(s). These results are discussed in terms of the structures of the two proteins and with respect to the physiological implications of the differences found.
The levels of vitamins A, E, B1, B2, folate, and B12 were measured in maternal blood, cord blood, and in 5-day neonate capillary blood samples. Twenty-six infants and their mothers served as controls and were compared with 32 low birth weight (LBW) infants. LBW infants showed significantly lower levels of vitamins A, E, B2, and folate than the controls. The folate status of mothers of LBW infants was significantly lower (7 +/- 1.8 ng/ml) than that of control mothers (21 +/- 0.8 ng/ml).
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The authors report a case of acute fungal arthritis following traumatic inoculation (bramble prick) in a 9 year-old boy. The implicated fungus was an highly pathogenic atypical strain of Scedosporium (monosporium) apiospermum. Two surgical operations (synovectomy and arthrodesis) and antifungal treatment with ketoconazole led to recovery. The pathogenic role of this fungus and especially the importance of toxic phenomena are discussed. This case is compared with other in the literature. The part of ketoconazole in the recovery of this patient is emphasized.
An 11-year-old child developed an infection of the scalp due to anaerobic germs following an acute attack of frontal sinusitis. The mechanism and therapy of this rare complication are discussed. The favorable outcome in this case suggests the need for revision of the generally poor prognosis of this complication, on the condition that adequate treatment be applied under the control of a multidisciplinary team.
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The transport of small molecules in the blood, normally assured by serum albumin in the adult, is not well known in the fetus since the albumin concentration is low in fetal serum and inversely related to the alpha 1-fetoprotein concentration. In order to investigate whether rat alpha 1-fetoprotein might be a fetal counterpart to albumin, the binding properties of these two proteins have been compared with respect to a series of molecules of biological importance, especially during fetal development: thyroid hormones and indole analogues. Though high-affinity binding of thyroxine was found with both rat alpha 1-fetoprotein and albumin, a significant difference in the number of binding sites for this hormone was found with the two proteins. Further, while rat serum albumin strongly bound L-tryptophan and indolyl-3-acetic acid (Ka approximately equal to 10(5) M-1), rat alpha 1-fetoprotein did not bind any of the indoles tested. These results are discussed with respect to the physiological and pharmacological significance of the transport role of these proteins.
An endogenous chromophore regularly associated with rat alpha 1 fetoprotein was detected by a systematic study of the fluorescence spectra of the protein purified by immunoabsorption. This fluorescent ligand, of low molecular weight, was dissociated from rat alpha 1 fetoprotein by exhaustive dialysis of the protein at low concentration. A phase partition method with aqueous preparations of rat alpha 1 fetoprotein allowed extraction of this chromophore into n-butanol and determination of its spectrofluorimetric characteristics: an excitation maximum at 305 nm and an emission maximum at 365 nm. We have also shown that this endogenous chromophore competed with estradiol-17 beta for the same binding sites in rat alpha 1 fetoprotein. In conclusion, the implication of a specific transport role of this protein for small ligands in fetal development is discussed.
In fetal or adult rats estradiol is carried in the plasma by alpha-fetoprotein or albumin. The protection of the carriers toward enzymatic oxidation by 17 beta-hydroxysteroid dehydrogenase from rat liver has been studied. Concentrations of carrier protein and estradiol were adjusted to give free estradiol concentrations varying from Km/10 to Km/100 and the ratio of the catalytic velocity to that observed for the same concentration of free estradiol in the absence of carrier protein were recorded. With alpha-fetoprotein the ratio fell as expected as the carrier concentration was increased, but with serum albumin the ratio was close to unity when the concentration of carrier protein was increased from 70 to 700 microM. Thus, a fetoprotein but not albumin protected the steroid against catalytic oxidation. Similar experiments were carried out replacing the mammalian enzyme by the dehydrogenase from Pseudomonas testosteroni, and in this case, both carrier proteins protected the substrate. The lack of protection by albumin against the dehydrogenation by the mammalian enzyme is discussed.
Redistribution of blood volume during orthostatism is followed by a reduction in venous return and therefore cardiac output. A drop in the blood pressure following postural changes is normally prevented by the action of the baroreceptor reflex, which leads to an increase in total peripheral resistance and heart rate. Orthostatic hypotension may arise from a variety of causes. In some cases, the disorder of postural regulation is due to an autonomic nervous system disease, and various tests are available that enable the diagnosis to be confirmed and the mechanism of action to be elucidated. Certain of these investigations explore the function of the complete baroreceptor reflex arc, while others enable selective study of either the efferent parasympathetic or sympathetic pathways. Central zones and afferent pathways cannot be explored directly. Individual tests are of limited value only, and the results of overall investigations are necessary for a better understanding and therefore more effective therapy of orthostatic hypotension due to autonomic nervous system disease.
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